chrX-106034293-T-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_000354.6(SERPINA7):c.986A>T(p.Tyr329Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0019 in 1,206,818 control chromosomes in the GnomAD database, including 7 homozygotes. There are 709 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 44 hem., cov: 23)

Exomes 𝑓: 0.0019 ( 7 hom. 665 hem. )

Consequence

SERPINA7
NM_000354.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.51

Publications

5 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: Likely_benign. The variant received -1 ACMG points.

PP5

Variant X-106034293-T-A is Pathogenic according to our data. Variant chrX-106034293-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 9792.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.08913022). . Strength limited to SUPPORTING due to the PP5.

BS2

High Hemizygotes in GnomAd4 at 44 XL geneVariant has number of hemizygotes 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA7	NM_000354.6	MANE Select	c.986A>T	p.Tyr329Phe	missense	Exon 4 of 5	NP_000345.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SERPINA7	ENST00000372563.2	TSL:5 MANE Select	c.986A>T	p.Tyr329Phe	missense	Exon 4 of 5	ENSP00000361644.1
SERPINA7	ENST00000327674.8	TSL:1	c.986A>T	p.Tyr329Phe	missense	Exon 3 of 4	ENSP00000329374.4
SERPINA7	ENST00000487487.1	TSL:3	n.259A>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

158

AN:

112087

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000421

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.00197

GnomAD2 exomes

AF:

0.00101

AC:

185

AN:

182839

AF XY:

0.00107

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.000658

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00195

AC:

2130

AN:

1094680

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

665

AN XY:

360250

show subpopulations

African (AFR)

AF:

0.000380

AC:

AN:

26324

American (AMR)

AF:

0.000597

AC:

AN:

35163

Ashkenazi Jewish (ASJ)

AF:

0.0000517

AC:

AN:

19348

East Asian (EAS)

AF:

0.00

AC:

AN:

30181

South Asian (SAS)

AF:

0.0000740

AC:

AN:

54056

European-Finnish (FIN)

AF:

0.0000987

AC:

AN:

40522

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00240

AC:

2015

AN:

838988

Other (OTH)

AF:

0.00161

AC:

AN:

45966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.00141

AC:

158

AN:

112138

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

34340

show subpopulations

African (AFR)

AF:

0.000421

AC:

AN:

30911

American (AMR)

AF:

0.00199

AC:

AN:

10572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.00

AC:

AN:

2707

European-Finnish (FIN)

AF:

0.000162

AC:

AN:

6157

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00226

AC:

120

AN:

53183

Other (OTH)

AF:

0.00195

AC:

AN:

1540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00163

Hom.:

Bravo

AF:

0.00134

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00277

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00297

AC:

ExAC

AF:

0.00101

AC:

122

EpiCase

AF:

0.00251

EpiControl

AF:

0.00214

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Thyroxine-binding globulin, Chicago (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.12

DEOGEN2

Benign

0.057

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.70

M_CAP

Benign

0.057

MetaRNN

Benign

0.089

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.4

PhyloP100

5.5

PrimateAI

Benign

0.41

PROVEAN

Benign

2.2

REVEL

Uncertain

0.38

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.69

MVP

0.45

MPC

0.025

ClinPred

0.0029

GERP RS

3.7

Varity_R

0.20

gMVP

0.43

Mutation Taster

=88/12

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over