X-106033506-T-G

Position:

chrX-106033506-T-G

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA7	NM_000354.6 linkuse as main transcript	c.1242A>C	p.Glu414Asp	missense_variant	5/5	ENST00000372563.2
SERPINA7	XM_006724683.3 linkuse as main transcript	c.1272A>C	p.Glu424Asp	missense_variant	5/5
SERPINA7	XM_005262180.5 linkuse as main transcript	c.*187A>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA7	ENST00000372563.2 linkuse as main transcript	c.1242A>C	p.Glu414Asp	missense_variant	5/5	5	NM_000354.6	P1
SERPINA7	ENST00000327674.8 linkuse as main transcript	c.1242A>C	p.Glu414Asp	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00479

AC:

536

AN:

111814

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

154

AN XY:

34028

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

GnomAD3 exomes

AF:

0.00152

AC:

277

AN:

182829

Hom.:

AF XY:

0.00107

AC XY:

AN XY:

67527

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 SAS exome

AF:

0.0000524

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

Gnomad4 AFR exome

AF:

0.0190

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.000999

GnomAD4 genome

AF:

0.00477

AC:

534

AN:

111864

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

154

AN XY:

34088

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.00199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.00198

Alfa

AF:

0.000648

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.019

T;T

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.20

.;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.17

Sift

Benign

0.29

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.17

Gain of phosphorylation at T413 (P = 0.1679);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over