2-45413189-G-C

Variant names:

• chr2-45413189-G-C
• NM_018079.5:c.2438C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018079.5(SRBD1):​c.2438C>G​(p.Ala813Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRBD1 NM_018079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12456632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRBD1	NM_018079.5	c.2438C>G	p.Ala813Gly	missense_variant	Exon 19 of 21	ENST00000263736.5	NP_060549.4
SRBD1	XM_011532946.3	c.2390C>G	p.Ala797Gly	missense_variant	Exon 19 of 21		XP_011531248.1
SRBD1	XM_047444861.1	c.995C>G	p.Ala332Gly	missense_variant	Exon 11 of 13		XP_047300817.1
SRBD1	XM_047444862.1	c.995C>G	p.Ala332Gly	missense_variant	Exon 10 of 12		XP_047300818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRBD1	ENST00000263736.5	c.2438C>G	p.Ala813Gly	missense_variant	Exon 19 of 21	2	NM_018079.5	ENSP00000263736.4
SRBD1	ENST00000490133.5	n.1335C>G		non_coding_transcript_exon_variant	Exon 4 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2438C>G (p.A813G) alteration is located in exon 19 (coding exon 18) of the SRBD1 gene. This alteration results from a C to G substitution at nucleotide position 2438, causing the alanine (A) at amino acid position 813 to be replaced by a glycine (G). 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	Benign	0.089
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.92
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.56	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.10
Sift	Benign	0.42	T
Sift4G	Benign	0.48	T
Polyphen		0.039	B
Vest4		0.088
MutPred		0.73		Gain of sheet (P = 0.0221);
MVP		0.18
MPC		0.013
ClinPred		0.22	T
GERP RS		3.6
Varity_R		0.063
gMVP		0.27

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: chr2-45640328;