Variant X-106033600-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000354.6(SERPINA7):c.1148C>T(p.Pro383Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,547 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SERPINA7
NM_000354.6 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 2.28

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA7	NM_000354.6 linkuse as main transcript	c.1148C>T	p.Pro383Leu	missense_variant	5/5	ENST00000372563.2
SERPINA7	XM_006724683.3 linkuse as main transcript	c.1178C>T	p.Pro393Leu	missense_variant	5/5
SERPINA7	XM_005262180.5 linkuse as main transcript	c.*93C>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.1148C>T	p.Pro383Leu	missense_variant	5/5	5	NM_000354.6	P1
SERPINA7	ENST00000327674.8 linkuse as main transcript	c.1148C>T	p.Pro383Leu	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182762

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67516

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097547

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363001

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Thyroxine-binding globulin quantitative trait locus

Other:1

association, no assertion criteria provided

literature only

OMIM

Feb 01, 1996

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.20

T;T

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.73

.;T

M_CAP

Pathogenic

0.61

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

9.2e-7

A;A

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Uncertain

0.53

Sift

Benign

0.035

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.61

P;P

Vest4

0.35

MutPred

0.76

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.70

MPC

0.17

ClinPred

0.26

GERP RS

2.2

Varity_R

0.28

gMVP

0.41

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