2-45418458-T-G

Position:

• chr2-45418458-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018079.5(SRBD1):​c.2240A>C​(p.Gln747Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRBD1 NM_018079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

Genes affected

SRBD1 (HGNC:25521): (S1 RNA binding domain 1) Predicted to enable mRNA binding activity. Predicted to be a structural constituent of ribosome. Predicted to be involved in translation. [provided by Alliance of Genome Resources, Apr 2022]

SRBD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRBD1	NM_018079.5	c.2240A>C	p.Gln747Pro	missense_variant	18/21	ENST00000263736.5	NP_060549.4
SRBD1	XM_011532946.3	c.2192A>C	p.Gln731Pro	missense_variant	18/21		XP_011531248.1
SRBD1	XM_047444861.1	c.797A>C	p.Gln266Pro	missense_variant	10/13		XP_047300817.1
SRBD1	XM_047444862.1	c.797A>C	p.Gln266Pro	missense_variant	9/12		XP_047300818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRBD1	ENST00000263736.5	c.2240A>C	p.Gln747Pro	missense_variant	18/21	2	NM_018079.5	ENSP00000263736.4
SRBD1	ENST00000475073.5	n.564A>C		non_coding_transcript_exon_variant	6/6	4
SRBD1	ENST00000490133.5	n.1137A>C		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 10, 2024

The c.2240A>C (p.Q747P) alteration is located in exon 18 (coding exon 17) of the SRBD1 gene. This alteration results from a A to C substitution at nucleotide position 2240, causing the glutamine (Q) at amino acid position 747 to be replaced by a proline (P). 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	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.9	H
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.48		Gain of glycosylation at Q747 (P = 0.0342);
MVP		0.74
MPC		0.090
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.91
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-45645597;