Variant rs1050086 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000354.6(SERPINA7):c.571G>C(p.Asp191His) 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 1,097,285 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D191N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

SERPINA7
NM_000354.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA7	NM_000354.6 linkuse as main transcript	c.571G>C	p.Asp191His	missense_variant	2/5	ENST00000372563.2	NP_000345.2	P05543
SERPINA7	XM_006724683.3 linkuse as main transcript	c.571G>C	p.Asp191His	missense_variant	2/5		XP_006724746.1
SERPINA7	XM_005262180.5 linkuse as main transcript	c.571G>C	p.Asp191His	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>C	p.Asp191His	missense_variant	2/5	5	NM_000354.6	ENSP00000361644.1		P05543
SERPINA7	ENST00000327674.8 linkuse as main transcript	c.571G>C	p.Asp191His	missense_variant	1/4	1		ENSP00000329374.4		P05543

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182890

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67526

show subpopulations

Gnomad AFR exome

AF:

0.0000760

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:

1097285

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362877

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.24

T;T

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.58

.;T

M_CAP

Pathogenic

0.53

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Uncertain

0.52

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.038

D;D

Polyphen

0.96

D;D

Vest4

0.13

MutPred

0.66

Loss of catalytic residue at D191 (P = 0.0055);Loss of catalytic residue at D191 (P = 0.0055);

MVP

0.68

MPC

0.031

ClinPred

0.30

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over