rs4820682

chr22-26488073-G-Achr22-26488073-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. 12/19 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. 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

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

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	UniProt
SRRD	NM_001013694.3	c.295G>A	p.Ala99Thr	missense_variant	3/7	ENST00000215917.11
SRRD	XM_011530178.3	c.82G>A	p.Ala28Thr	missense_variant	3/7
SRRD	XM_017028799.3	c.295G>A	p.Ala99Thr	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRRD	ENST00000215917.11	c.295G>A	p.Ala99Thr	missense_variant	3/7	1	NM_001013694.3	P1
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
MutationTaster	Benign	1.0	P
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;