Variant rs28937312 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_000354.6(SERPINA7):c.740T>C(p.Leu247Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,608 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes 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: 0.0000036 ( 0 hom. 2 hem. )

Consequence

SERPINA7
NM_000354.6 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.484

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 Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA7	NM_000354.6 linkuse as main transcript	c.740T>C	p.Leu247Pro	missense_variant	3/5	ENST00000372563.2
SERPINA7	XM_006724683.3 linkuse as main transcript	c.740T>C	p.Leu247Pro	missense_variant	3/5
SERPINA7	XM_005262180.5 linkuse as main transcript	c.740T>C	p.Leu247Pro	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA7	ENST00000372563.2 linkuse as main transcript	c.740T>C	p.Leu247Pro	missense_variant	3/5	5	NM_000354.6	P1
SERPINA7	ENST00000327674.8 linkuse as main transcript	c.740T>C	p.Leu247Pro	missense_variant	2/4	1		P1
SERPINA7	ENST00000487487.1 linkuse as main transcript	n.13T>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182846

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67564

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1097608

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

363110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000356

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

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

Mar 01, 1992

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

FATHMM_MKL

Benign

0.28

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

0.000021

A;A

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.63

Sift

Benign

0.13

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.83

P;P

Vest4

0.64

MutPred

0.88

Loss of stability (P = 0.0238);Loss of stability (P = 0.0238);

MVP

0.93

MPC

0.24

ClinPred

0.87

GERP RS

3.2

Varity_R

0.96

gMVP

0.95

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