Variant 22-26484030-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001013694.3(SRRD):c.140C>T(p.Ala47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000721 in 816,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00074 ( 0 hom. )

Consequence

SRRD
NM_001013694.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.884

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 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=0.026937038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRD	NM_001013694.3 linkuse as main transcript	c.140C>T	p.Ala47Val	missense_variant	1/7	ENST00000215917.11	NP_001013716.2	Q9UH36
SRRD	XM_017028799.3 linkuse as main transcript	c.140C>T	p.Ala47Val	missense_variant	1/6		XP_016884288.1
SRRD	XM_011530178.3 linkuse as main transcript	c.-120C>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.140C>T	p.Ala47Val	missense_variant	1/7	1	NM_001013694.3	ENSP00000215917.6		Q9UH36

Frequencies

GnomAD3 genomes

AF:

0.000508

AC:

AN:

74730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000254

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00305

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000642

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000262

AC:

AN:

64934

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

37554

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:

0.00

Gnomad FIN exome

AF:

0.000254

Gnomad NFE exome

AF:

0.000688

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000743

AC:

551

AN:

742062

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

269

AN XY:

371188

show subpopulations

Gnomad4 AFR exome

AF:

0.000111

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000288

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00180

Gnomad4 NFE exome

AF:

0.000865

Gnomad4 OTH exome

AF:

0.000402

GnomAD4 genome

AF:

0.000508

AC:

AN:

74820

Hom.:

Cov.:

AF XY:

0.000691

AC XY:

AN XY:

36154

show subpopulations

Gnomad4 AFR

AF:

0.000172

Gnomad4 AMR

AF:

0.000254

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00305

Gnomad4 NFE

AF:

0.000642

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000208

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

Feb 16, 2023

The c.140C>T (p.A47V) 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 140, causing the alanine (A) at amino acid position 47 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.44

M_CAP

Benign

0.049

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.060

REVEL

Benign

0.037

Sift

Benign

0.35

Sift4G

Benign

0.77

Polyphen

0.0090

Vest4

0.20

MVP

0.25

MPC

0.025

ClinPred

0.064

GERP RS

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.024

gMVP

0.17

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