Variant X-106036488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000354.6(SERPINA7):c.571G>A(p.Asp191Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,208,900 control chromosomes in the GnomAD database, including 265 homozygotes. There are 1,982 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.031 ( 140 hom., 956 hem., cov: 22)

Exomes 𝑓: 0.0034 ( 125 hom. 1026 hem. )

Consequence

SERPINA7
NM_000354.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.0800

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018774569).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA7	NM_000354.6 linkuse as main transcript	c.571G>A	p.Asp191Asn	missense_variant	2/5	ENST00000372563.2	NP_000345.2	P05543
SERPINA7	XM_006724683.3 linkuse as main transcript	c.571G>A	p.Asp191Asn	missense_variant	2/5		XP_006724746.1
SERPINA7	XM_005262180.5 linkuse as main transcript	c.571G>A	p.Asp191Asn	missense_variant	2/5		XP_005262237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA7	ENST00000372563.2 linkuse as main transcript	c.571G>A	p.Asp191Asn	missense_variant	2/5	5	NM_000354.6	ENSP00000361644.1		P05543
SERPINA7	ENST00000327674.8 linkuse as main transcript	c.571G>A	p.Asp191Asn	missense_variant	1/4	1		ENSP00000329374.4		P05543

Frequencies

GnomAD3 genomes

AF:

0.0314

AC:

3503

AN:

111560

Hom.:

140

Cov.:

AF XY:

0.0282

AC XY:

953

AN XY:

33828

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

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:

0.000395

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.00922

AC:

1687

AN:

182890

Hom.:

AF XY:

0.00656

AC XY:

443

AN XY:

67526

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.00742

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000331

Gnomad OTH exome

AF:

0.00421

GnomAD4 exome

AF:

0.00344

AC:

3779

AN:

1097283

Hom.:

125

Cov.:

AF XY:

0.00283

AC XY:

1026

AN XY:

362877

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.00816

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000296

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00803

GnomAD4 genome

AF:

0.0314

AC:

3507

AN:

111617

Hom.:

140

Cov.:

AF XY:

0.0282

AC XY:

956

AN XY:

33895

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000395

Gnomad4 OTH

AF:

0.0264

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.0364

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.105

AC:

401

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.0103

AC:

1244

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Thyroxine-binding globulin, slow

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 1990

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.084

T;T

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.44

.;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.12

Sift

Benign

0.28

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0050

B;B

Vest4

0.045

MPC

0.027

ClinPred

0.0052

GERP RS

2.7

Varity_R

0.30

gMVP

0.25

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