NM_000354.6:c.1242A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBS1BS2_Supporting

The NM_000354.6(SERPINA7):c.1242A>C(p.Glu414Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000944 in 1,209,264 control chromosomes in the GnomAD database, including 10 homozygotes. There are 343 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 6 hom., 154 hem., cov: 23)

Exomes 𝑓: 0.00055 ( 4 hom. 189 hem. )

Consequence

SERPINA7
NM_000354.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.778

Publications

1 publications found

Variant links:

Genes affected

SERPINA7 (HGNC:11583): (serpin family A member 7) There are three proteins including thyroxine-binding globulin (TBG), transthyretin and albumin responsible for carrying the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in the bloodstream. This gene encodes the major thyroid hormone transport protein, TBG, in serum. It belongs to the serpin family in genomics, but the protein has no inhibitory function like many other members of the serpin family. Mutations in this gene result in TGB deficiency, which has been classified as partial deficiency, complete deficiency, and excess, based on the level of serum TBG. Alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of these variants has not been determined.[provided by RefSeq, Jun 2012]

SERPINA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030000508).

BP6

Variant X-106033506-T-G is Benign according to our data. Variant chrX-106033506-T-G is described in ClinVar as Benign. ClinVar VariationId is 777816.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00477 (534/111864) while in subpopulation AFR AF = 0.0164 (506/30805). AF 95% confidence interval is 0.0152. There are 6 homozygotes in GnomAd4. There are 154 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 XL geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000354.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA7	NM_000354.6	MANE Select	c.1242A>C	p.Glu414Asp	missense	Exon 5 of 5	NP_000345.2	P05543

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINA7	ENST00000372563.2	TSL:5 MANE Select	c.1242A>C	p.Glu414Asp	missense	Exon 5 of 5	ENSP00000361644.1	P05543
SERPINA7	ENST00000327674.8	TSL:1	c.1242A>C	p.Glu414Asp	missense	Exon 4 of 4	ENSP00000329374.4	P05543
SERPINA7	ENST00000907820.1		c.1272A>C	p.Glu424Asp	missense	Exon 5 of 5	ENSP00000577879.1

Frequencies

GnomAD3 genomes

AF:

0.00479

AC:

536

AN:

111814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00200

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000753

Gnomad OTH

AF:

0.00200

GnomAD2 exomes

AF:

0.00152

AC:

277

AN:

182829

AF XY:

0.00107

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.000553

AC:

607

AN:

1097400

Hom.:

Cov.:

AF XY:

0.000521

AC XY:

189

AN XY:

362948

show subpopulations

African (AFR)

AF:

0.0190

AC:

502

AN:

26360

American (AMR)

AF:

0.00131

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19365

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40517

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.0000143

AC:

AN:

841431

Other (OTH)

AF:

0.000999

AC:

AN:

46064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00477

AC:

534

AN:

111864

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

154

AN XY:

34088

show subpopulations

African (AFR)

AF:

0.0164

AC:

506

AN:

30805

American (AMR)

AF:

0.00199

AC:

AN:

10534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3515

South Asian (SAS)

AF:

0.00

AC:

AN:

2666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000753

AC:

AN:

53137

Other (OTH)

AF:

0.00198

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00609

ESP6500AA

AF:

0.0156

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00153

AC:

186

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.1

PhyloP100

0.78

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

REVEL

Benign

0.17

Sift

Benign

0.29

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.11

MutPred

0.17

Gain of phosphorylation at T413 (P = 0.1679)

MVP

0.33

MPC

0.024

ClinPred

0.0020

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.16

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over