rs4820682

Positions:

• chr22-26488073-G-A
• chr22-26488073-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013694.3(SRRD):​c.295G>A​(p.Ala99Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,613,368 control chromosomes in the GnomAD database, including 618,201 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.83 (52709 hom., cov: 32)
  • Exomes 𝑓: 0.88 (565492 hom.)
• Consequence: SRRD NM_001013694.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.2573106E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRD	NM_001013694.3	c.295G>A	p.Ala99Thr	missense_variant	3/7	ENST00000215917.11	NP_001013716.2
SRRD	XM_011530178.3	c.82G>A	p.Ala28Thr	missense_variant	3/7		XP_011528480.1
SRRD	XM_017028799.3	c.295G>A	p.Ala99Thr	missense_variant	3/6		XP_016884288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRRD	ENST00000215917.11	c.295G>A	p.Ala99Thr	missense_variant	3/7	1	NM_001013694.3	ENSP00000215917.6
SRRD	ENST00000477945.1	n.92G>A		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125802 AN: 152084 Hom.: 52690 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.836

GnomAD3 exomes AF: 0.871 AC: 216675 AN: 248666 Hom.: 94868 AF XY: 0.877 AC XY: 118276 AN XY: 134940

Gnomad AFR exome AF: 0.676

Gnomad AMR exome AF: 0.879

Gnomad ASJ exome AF: 0.844

Gnomad EAS exome AF: 0.793

Gnomad SAS exome AF: 0.901

Gnomad FIN exome AF: 0.954

Gnomad NFE exome AF: 0.886

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.879 AC: 1283763 AN: 1461166 Hom.: 565492 Cov.: 52 AF XY: 0.880 AC XY: 639952 AN XY: 726848

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.878

Gnomad4 ASJ exome AF: 0.839

Gnomad4 EAS exome AF: 0.772

Gnomad4 SAS exome AF: 0.905

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.885

Gnomad4 OTH exome AF: 0.868

GnomAD4 genome AF: 0.827 AC: 125870 AN: 152202 Hom.: 52709 Cov.: 32 AF XY: 0.831 AC XY: 61815 AN XY: 74420

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.834

Alfa AF: 0.871 Hom.: 141004

Bravo AF: 0.810

TwinsUK AF: 0.878 AC: 3255

ALSPAC AF: 0.877 AC: 3380

ESP6500AA AF: 0.684 AC: 2527

ESP6500EA AF: 0.884 AC: 7237

ExAC AF: 0.868 AC: 104835

Asia WGS AF: 0.818 AC: 2845 AN: 3478

EpiCase AF: 0.888

EpiControl AF: 0.882

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.7
DANN	Benign	0.90
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	9.3e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.050
Sift	Benign	0.30	T
Sift4G	Benign	0.26	T
Polyphen		0.0010	B
Vest4		0.029
MPC		0.026
ClinPred		0.0029	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.15

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

Other links and lift over

dbSNP: rs4820682; hg19: chr22-26884039;