2-45413256-C-G

Variant names:

• chr2-45413256-C-G
• rs142081663
• NM_018079.5:c.2371G>C

Variant summary

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

The NM_018079.5(SRBD1):​c.2371G>C​(p.Ala791Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A791T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SRBD1 NM_018079.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=0.07649508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRBD1	NM_018079.5	c.2371G>C	p.Ala791Pro	missense_variant	Exon 19 of 21	ENST00000263736.5	NP_060549.4
SRBD1	XM_011532946.3	c.2323G>C	p.Ala775Pro	missense_variant	Exon 19 of 21		XP_011531248.1
SRBD1	XM_047444861.1	c.928G>C	p.Ala310Pro	missense_variant	Exon 11 of 13		XP_047300817.1
SRBD1	XM_047444862.1	c.928G>C	p.Ala310Pro	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.2371G>C	p.Ala791Pro	missense_variant	Exon 19 of 21	2	NM_018079.5	ENSP00000263736.4
SRBD1	ENST00000490133.5	n.1268G>C		non_coding_transcript_exon_variant	Exon 4 of 6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250936 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461662 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.57
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.076
Sift	Benign	0.21	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.56		Loss of catalytic residue at A791 (P = 0.0417);
MVP		0.30
MPC		0.014
ClinPred		0.038	T
GERP RS		1.6
Varity_R		0.057
gMVP		0.54

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: rs142081663; hg19: chr2-45640395;