Variant X-106033504-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_000354.6(SERPINA7):c.1244C>T(p.Ala415Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000951 in 1,208,700 control chromosomes in the GnomAD database, including 1 homozygotes. There are 40 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 1 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000089 ( 0 hom. 39 hem. )

Consequence

SERPINA7
NM_000354.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0880

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008925915).

BP6

Variant X-106033504-G-A is Benign according to our data. Variant chrX-106033504-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661129.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 39 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
SERPINA7	NM_000354.6 linkuse as main transcript	c.1244C>T	p.Ala415Val	missense_variant	5/5	ENST00000372563.2
SERPINA7	XM_006724683.3 linkuse as main transcript	c.1274C>T	p.Ala425Val	missense_variant	5/5
SERPINA7	XM_005262180.5 linkuse as main transcript	c.*189C>T		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.1244C>T	p.Ala415Val	missense_variant	5/5	5	NM_000354.6	P1
SERPINA7	ENST00000327674.8 linkuse as main transcript	c.1244C>T	p.Ala415Val	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

111558

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33804

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000953

Gnomad ASJ

AF:

0.00455

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.000669

GnomAD3 exomes

AF:

0.000148

AC:

AN:

182803

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

67515

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.0000893

AC:

AN:

1097142

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

362700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000152

AC:

AN:

111558

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33804

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000953

Gnomad4 ASJ

AF:

0.00455

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.000669

Alfa

AF:

0.000521

Hom.:

Bravo

AF:

0.000166

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

SERPINA7: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.66

DANN

Benign

0.92

DEOGEN2

Benign

0.025

T;T

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.37

.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.0089

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.20

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.043

D;D

Polyphen

0.0

B;B

Vest4

0.023

MVP

0.43

MPC

0.025

ClinPred

0.022

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.13

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