22-26488073-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013694.3(SRRD):​c.295G>C​(p.Ala99Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 32)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040513217).

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>C	p.Ala99Pro	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>C	p.Ala99Pro	missense	Exon 3 of 7	ENSP00000215917.6
	SRRD	ENST00000477945.1	TSL:5	n.92G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.4
DANN	Benign	0.79
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.0050
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.020
Sift	Benign	0.33	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.17
MutPred		0.29		Gain of disorder (P = 0.0537)
MVP		0.16
MPC		0.029
ClinPred		0.053	T
GERP RS		-2.1
Varity_R		0.071
gMVP		0.24
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;