16-4207312-C-A

Position:

• chr16-4207312-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098814.2(SRL):​c.62-2678G>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SRL NM_001098814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

Genes affected

SRL (HGNC:11295): (sarcalumenin) Predicted to enable GTP binding activity. Predicted to be involved in endocytosis and endosomal transport. Predicted to act upstream of or within response to muscle activity involved in regulation of muscle adaptation and store-operated calcium entry. Predicted to be located in sarcoplasmic reticulum lumen and sarcoplasmic reticulum membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRL	NM_001098814.2	c.62-2678G>T		intron_variant		ENST00000399609.7	NP_001092284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRL	ENST00000399609.7	c.62-2678G>T		intron_variant		1	NM_001098814.2	ENSP00000382518	P1
SRL	ENST00000572111.1	c.854G>T	p.Ser285Ile	missense_variant, NMD_transcript_variant	2/7	1		ENSP00000461179
SRL	ENST00000537996.1	c.-65-2678G>T		intron_variant		2		ENSP00000440350

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Uncertain	0.99

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: rs75825892; hg19: chr16-4257313;