chr2-45389525-T-C

Variant names:

• chr2-45389525-T-C
• NM_018079.5:c.2773A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018079.5(SRBD1):​c.2773A>G​(p.Lys925Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 4.62
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32086653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRBD1	NM_018079.5	MANE Select	c.2773A>G	p.Lys925Glu	missense	Exon 21 of 21	NP_060549.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRBD1	ENST00000263736.5	TSL:2 MANE Select	c.2773A>G	p.Lys925Glu	missense	Exon 21 of 21	ENSP00000263736.4	Q8N5C6-1
	SRBD1	ENST00000922966.1		c.2773A>G	p.Lys925Glu	missense	Exon 21 of 21	ENSP00000593025.1
	SRBD1	ENST00000490133.5	TSL:2	n.1670A>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0056	T
Eigen	Benign	0.055
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.12	B
Vest4		0.31
MutPred		0.51		Loss of ubiquitination at K925 (P = 0.0192)
MVP		0.60
MPC		0.054
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.23
gMVP		0.66
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

hg19: chr2-45616664;