19-40441953-C-T

Position:

chr19-40441953-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_203344.3(SERTAD3):c.128G>A(p.Arg43His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,570,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

SERTAD3
NM_203344.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.101

Variant links:

Genes affected

SERTAD3 (HGNC:17931): (SERTA domain containing 3) The protein encoded by this gene was identified in a yeast two-hybrid assay employing the second subunit of human replication protein A as bait. It is localized to the nucleus and its expression is significantly higher in cancer cell lines compared to normal cell lines. This protein has also been shown to be a strong transcriptional co-activator. Alternative splicing has been observed at this locus and two variants, both encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SERTAD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045993835).

BP6

Variant 19-40441953-C-T is Benign according to our data. Variant chr19-40441953-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2228165.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERTAD3	NM_203344.3 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	2/2	ENST00000322354.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERTAD3	ENST00000322354.4 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	2/2	1	NM_203344.3	P1
SERTAD3	ENST00000392028.8 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	2/2	1		P1
SERTAD3	ENST00000599706.1 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	2/2	2
SERTAD3	ENST00000596456.1 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000382

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000104

AC:

AN:

210720

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

113050

show subpopulations

Gnomad AFR exome

AF:

0.0000635

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:

0.000197

Gnomad OTH exome

AF:

0.000400

GnomAD4 exome

AF:

0.000276

AC:

391

AN:

1418164

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

205

AN XY:

701816

show subpopulations

Gnomad4 AFR exome

AF:

0.0000934

Gnomad4 AMR exome

AF:

0.0000268

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:

0.000346

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.000217

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00192

Alfa

AF:

0.000354

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.057

T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.42

M_CAP

Benign

0.0011

MetaRNN

Benign

0.046

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;.

MutationTaster

Benign

0.71

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.39

N;N;.;.

REVEL

Benign

0.039

Sift

Benign

0.55

T;T;.;.

Sift4G

Pathogenic

0.0

D;D;.;.

Polyphen

0.0030

B;B;.;.

Vest4

0.068

MVP

0.13

MPC

0.22

ClinPred

0.023

GERP RS

-0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.022

gMVP

0.16

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