NM_000354.6:c.571G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP5BP4BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

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

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PP5

Variant X-106036488-C-T is Pathogenic according to our data. Variant chrX-106036488-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 9786.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018774569). . Strength limited to SUPPORTING due to the PP5.

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 rank	MANE	Protein	UniProt
SERPINA7	NM_000354.6 link	c.571G>A	p.Asp191Asn	missense_variant	Exon 2 of 5	ENST00000372563.2	NP_000345.2	P05543
SERPINA7	XM_006724683.3 link	c.571G>A	p.Asp191Asn	missense_variant	Exon 2 of 5		XP_006724746.1
SERPINA7	XM_005262180.5 link	c.571G>A	p.Asp191Asn	missense_variant	Exon 2 of 5		XP_005262237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA7	ENST00000372563.2 link	c.571G>A	p.Asp191Asn	missense_variant	Exon 2 of 5	5	NM_000354.6	ENSP00000361644.1		P05543
SERPINA7	ENST00000327674.8 link	c.571G>A	p.Asp191Asn	missense_variant	Exon 1 of 4	1		ENSP00000329374.4		P05543

Frequencies

GnomAD3 genomes

AF:

0.0314

AC:

3503

AN:

111560

Hom.:

140

Cov.:

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

GnomAD2 exomes

AF:

0.00922

AC:

1687

AN:

182890

AF XY:

0.00656

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 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

African (AFR)

AF:

0.111

AC:

2915

AN:

26360

American (AMR)

AF:

0.00816

AC:

287

AN:

35178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19353

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.000296

AC:

AN:

54101

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40522

Middle Eastern (MID)

AF:

0.00460

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.000204

AC:

172

AN:

841383

Other (OTH)

AF:

0.00803

AC:

370

AN:

46054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

145

291

436

582

727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0314

AC:

3507

AN:

111617

Hom.:

140

Cov.:

AF XY:

0.0282

AC XY:

956

AN XY:

33895

show subpopulations

African (AFR)

AF:

0.108

AC:

3307

AN:

30685

American (AMR)

AF:

0.0131

AC:

138

AN:

10521

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3510

South Asian (SAS)

AF:

0.00

AC:

AN:

2669

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6065

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000395

AC:

AN:

53105

Other (OTH)

AF:

0.0264

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

114

228

342

456

570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0104

Hom.:

421

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

Apr 01, 1990

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

-0.080

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

Mutation Taster

=98/2

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_000354.6:c.571G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over