2-45418539-T-C

Position:

• chr2-45418539-T-C

Variant summary

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

The NM_018079.5(SRBD1):​c.2159A>G​(p.His720Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRBD1 NM_018079.5 missense, splice_region
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRBD1	NM_018079.5	c.2159A>G	p.His720Arg	missense_variant, splice_region_variant	18/21	ENST00000263736.5
SRBD1	XM_011532946.3	c.2111A>G	p.His704Arg	missense_variant, splice_region_variant	18/21
SRBD1	XM_047444861.1	c.716A>G	p.His239Arg	missense_variant, splice_region_variant	10/13
SRBD1	XM_047444862.1	c.716A>G	p.His239Arg	missense_variant, splice_region_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRBD1	ENST00000263736.5	c.2159A>G	p.His720Arg	missense_variant, splice_region_variant	18/21	2	NM_018079.5	P1
SRBD1	ENST00000475073.5	n.483A>G		splice_region_variant, non_coding_transcript_exon_variant	6/6	4
SRBD1	ENST00000490133.5	n.1056A>G		splice_region_variant, 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

Aug 02, 2021

The c.2159A>G (p.H720R) alteration is located in exon 18 (coding exon 17) of the SRBD1 gene. This alteration results from a A to G substitution at nucleotide position 2159, causing the histidine (H) at amino acid position 720 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.32
Sift	Benign	0.35	T
Sift4G	Benign	0.36	T
Polyphen		0.82	P
Vest4		0.82
MutPred		0.52		Gain of MoRF binding (P = 0.0177);
MVP		0.52
MPC		0.029
ClinPred		0.95	D
GERP RS		5.9
Varity_R		0.55
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-45645678;