Variant X-106034293-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_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. 13/20 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

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 Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08913022).

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINA7	NM_000354.6 linkuse as main transcript	c.986A>T	p.Tyr329Phe	missense_variant	4/5	ENST00000372563.2	NP_000345.2
SERPINA7	XM_006724683.3 linkuse as main transcript	c.986A>T	p.Tyr329Phe	missense_variant	4/5		XP_006724746.1
SERPINA7	XM_005262180.5 linkuse as main transcript	c.986A>T	p.Tyr329Phe	missense_variant	4/5		XP_005262237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SERPINA7	ENST00000372563.2 linkuse as main transcript	c.986A>T	p.Tyr329Phe	missense_variant	4/5	5	NM_000354.6	ENSP00000361644	P1
SERPINA7	ENST00000327674.8 linkuse as main transcript	c.986A>T	p.Tyr329Phe	missense_variant	3/4	1		ENSP00000329374	P1
SERPINA7	ENST00000487487.1 linkuse as main transcript	n.259A>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

158

AN:

112087

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

34279

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

GnomAD3 exomes

AF:

0.00101

AC:

185

AN:

182839

Hom.:

AF XY:

0.00107

AC XY:

AN XY:

67523

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 SAS exome

AF:

0.0000525

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

Gnomad4 AFR exome

AF:

0.000380

Gnomad4 AMR exome

AF:

0.000597

Gnomad4 ASJ exome

AF:

0.0000517

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000740

Gnomad4 FIN exome

AF:

0.0000987

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00141

AC:

158

AN:

112138

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

34340

show subpopulations

Gnomad4 AFR

AF:

0.000421

Gnomad4 AMR

AF:

0.00199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000162

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.00195

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Thyroxine-binding globulin, Chicago

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 24, 1995

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.12

DEOGEN2

Benign

0.057

T;T

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.4

N;N

MutationTaster

Benign

0.18

A;A

PrimateAI

Benign

0.41

PROVEAN

Benign

2.2

N;N

REVEL

Uncertain

0.38

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.69

MVP

0.45

MPC

0.025

ClinPred

0.0029

GERP RS

3.7

Varity_R

0.20

gMVP

0.43

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

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