Variant 22-26484009-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001013694.3(SRRD):c.119C>T(p.Ala40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,340,756 control chromosomes in the GnomAD database, including 3 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00012 ( 3 hom. )

Consequence

SRRD
NM_001013694.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.696

Variant links:

Genes affected

SRRD (HGNC:33910): (SRR1 domain containing) Predicted to be involved in microtubule-based process; regulation of circadian rhythm; and regulation of heme biosynthetic process. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SRRD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013597041).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRD	NM_001013694.3 linkuse as main transcript	c.119C>T	p.Ala40Val	missense_variant	1/7	ENST00000215917.11	NP_001013716.2	Q9UH36
SRRD	XM_017028799.3 linkuse as main transcript	c.119C>T	p.Ala40Val	missense_variant	1/6		XP_016884288.1
SRRD	XM_011530178.3 linkuse as main transcript	c.-141C>T		5_prime_UTR_variant	1/7		XP_011528480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRRD	ENST00000215917.11 linkuse as main transcript	c.119C>T	p.Ala40Val	missense_variant	1/7	1	NM_001013694.3	ENSP00000215917.6		Q9UH36

Frequencies

GnomAD3 genomes

AF:

0.000575

AC:

AN:

146132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000605

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00161

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000305

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000269

AC:

AN:

22326

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

13512

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:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.000117

AC:

140

AN:

1194488

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

581424

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.000660

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000383

Gnomad4 SAS exome

AF:

0.00163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000611

Gnomad4 OTH exome

AF:

0.000351

GnomAD4 genome

AF:

0.000574

AC:

AN:

146268

Hom.:

Cov.:

AF XY:

0.000547

AC XY:

AN XY:

71322

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.000604

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00161

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000305

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000990

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.119C>T (p.A40V) alteration is located in exon 1 (coding exon 1) of the SRRD gene. This alteration results from a C to T substitution at nucleotide position 119, causing the alanine (A) at amino acid position 40 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.013

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.31

M_CAP

Benign

0.0028

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.32

REVEL

Benign

0.0020

Sift

Benign

0.23

Sift4G

Benign

0.54

Vest4

0.12

MutPred

0.24

Loss of helix (P = 0.079);

MVP

0.19

MPC

0.025

ClinPred

0.063

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.069

gMVP

0.18

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