rs4820682

Variant names:

• chr22-26488073-G-A
• rs4820682
• NM_001013694.3:c.295G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A99D) has been classified as Uncertain significance.

• 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
• Publications: 33 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013694.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRD	NM_001013694.3	MANE Select	c.295G>A	p.Ala99Thr	missense	Exon 3 of 7	NP_001013716.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRD	ENST00000215917.11	TSL:1 MANE Select	c.295G>A	p.Ala99Thr	missense	Exon 3 of 7	ENSP00000215917.6
	SRRD	ENST00000477945.1	TSL:5	n.92G>A		non_coding_transcript_exon	Exon 1 of 4

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

GnomAD2 exomes AF: 0.871 AC: 216675 AN: 248666 AF XY: 0.877

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 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

African (AFR) AF: 0.673 AC: 22490 AN: 33426

American (AMR) AF: 0.878 AC: 39165 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 21894 AN: 26110

East Asian (EAS) AF: 0.772 AC: 30654 AN: 39696

South Asian (SAS) AF: 0.905 AC: 77962 AN: 86102

European-Finnish (FIN) AF: 0.947 AC: 50590 AN: 53408

Middle Eastern (MID) AF: 0.886 AC: 5102 AN: 5758

European-Non Finnish (NFE) AF: 0.885 AC: 983530 AN: 1111718

Other (OTH) AF: 0.868 AC: 52376 AN: 60366

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

African (AFR) AF: 0.679 AC: 28153 AN: 41478

American (AMR) AF: 0.855 AC: 13070 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2914 AN: 3470

East Asian (EAS) AF: 0.793 AC: 4100 AN: 5170

South Asian (SAS) AF: 0.891 AC: 4306 AN: 4832

European-Finnish (FIN) AF: 0.956 AC: 10150 AN: 10622

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60409 AN: 68024

Other (OTH) AF: 0.834 AC: 1763 AN: 2114

Alfa AF: 0.861 Hom.: 172990

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 v4.9

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
PhyloP100		-0.0050
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4820682; hg19: chr22-26884039; COSMIC: COSV107233611; COSMIC: COSV107233611;