Genetic Variant SERTAD4:p.Arg51Gln (chr1-210238112-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019605.5(SERTAD4):c.152G>A(p.Arg51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,609,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SERTAD4
NM_019605.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Variant links:

Genes affected

SERTAD4 (HGNC:25236): (SERTA domain containing 4) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SERTAD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029020697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERTAD4	NM_019605.5 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 4	ENST00000367012.4	NP_062551.1	Q9NUC0
SERTAD4	NM_001375428.1 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 4		NP_001362357.1
SERTAD4	NM_001354173.2 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 5		NP_001341102.1
SERTAD4	XM_047425536.1 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 5		XP_047281492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERTAD4	ENST00000367012.4 link	c.152G>A	p.Arg51Gln	missense_variant	Exon 2 of 4	1	NM_019605.5	ENSP00000355979.3	Q9NUC0
SERTAD4	ENST00000482421.1 link	n.170G>A		non_coding_transcript_exon_variant	Exon 1 of 4	3
SERTAD4	ENST00000483884.1 link	n.135G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
SERTAD4	ENST00000490620.5 link	n.356G>A		non_coding_transcript_exon_variant	Exon 2 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000183

AC:

AN:

245752

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

133020

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000419

Gnomad NFE exome

AF:

0.000288

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000105

AC:

153

AN:

1456994

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

724882

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000584

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000874

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152G>A (p.R51Q) alteration is located in exon 2 (coding exon 1) of the SERTAD4 gene. This alteration results from a G to A substitution at nucleotide position 152, causing the arginine (R) at amino acid position 51 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0081

Eigen

Benign

-0.16

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.0029

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.47

REVEL

Benign

0.037

Sift

Benign

0.036

Sift4G

Uncertain

0.056

Polyphen

0.016

Vest4

0.22

MVP

0.043

MPC

0.10

ClinPred

0.037

GERP RS

4.5

Varity_R

0.087

gMVP

0.24

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