chr2-45389525-T-C

Position:

• chr2-45389525-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRBD1	NM_018079.5	c.2773A>G	p.Lys925Glu	missense_variant	21/21	ENST00000263736.5
SRBD1	XM_011532946.3	c.2725A>G	p.Lys909Glu	missense_variant	21/21
SRBD1	XM_047444861.1	c.1330A>G	p.Lys444Glu	missense_variant	13/13
SRBD1	XM_047444862.1	c.1330A>G	p.Lys444Glu	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRBD1	ENST00000263736.5	c.2773A>G	p.Lys925Glu	missense_variant	21/21	2	NM_018079.5	P1
SRBD1	ENST00000490133.5	n.1670A>G		non_coding_transcript_exon_variant	6/6	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.2773A>G (p.K925E) alteration is located in exon 21 (coding exon 20) of the SRBD1 gene. This alteration results from a A to G substitution at nucleotide position 2773, causing the lysine (K) at amino acid position 925 to be replaced by a glutamic acid (E). 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	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
MutationTaster	Benign	0.98	D;D
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

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: chr2-45616664;