rs118131979

Variant names:

• chr19-16482507-C-A
• rs118131979
• NM_145046.5:c.861G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-16482507-C-A
• chr19-16482507-C-G
• chr19-16482507-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145046.5(CALR3):​c.861G>T​(p.Thr287Thr) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. T287T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALR3 NM_145046.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.85
• Publications: 4 publications found

Genes affected

CALR3 (HGNC:20407): (calreticulin 3) The protein encoded by this gene belongs to the calreticulin family, members of which are calcium-binding chaperones localized mainly in the endoplasmic reticulum. This protein is also localized to the endoplasmic reticulum lumen, however, its capacity for calcium-binding may be absent or much lower than other family members. This gene is specifically expressed in the testis, and may be required for sperm fertility. Mutation in this gene has been associated with familial hypertrophic cardiomyopathy. [provided by RefSeq, Dec 2011]

CALR3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000141979 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-7.85 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALR3	NM_145046.5	MANE Select	c.861G>T	p.Thr287Thr	synonymous	Exon 7 of 9	NP_659483.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALR3	ENST00000269881.8	TSL:1 MANE Select	c.861G>T	p.Thr287Thr	synonymous	Exon 7 of 9	ENSP00000269881.3
	ENSG00000141979	ENST00000409035.1	TSL:2	n.*664G>T		non_coding_transcript_exon	Exon 10 of 12	ENSP00000386951.2
	ENSG00000141979	ENST00000409035.1	TSL:2	n.*664G>T		3_prime_UTR	Exon 10 of 12	ENSP00000386951.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 27

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.010
DANN	Benign	0.42
PhyloP100		-7.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

dbSNP: rs118131979; hg19: chr19-16593318;