rs371617212

Variant names:

• chr19-5914706-C-A
• NM_004058.5:c.227C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-5914706-C-A
• chr19-5914706-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004058.5(CAPS):​c.227C>A​(p.Thr76Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CAPS NM_004058.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

CAPS (HGNC:1487): (calcyphosine) This gene encodes a calcium-binding protein, which may play a role in the regulation of ion transport. A similar protein was first described as a potentially important regulatory protein in the dog thyroid and was termed as R2D5 antigen in rabbit. Alternative splicing of this gene generates two transcript variants. [provided by RefSeq, Jul 2008]

ENSG00000267314 (HGNC:):

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=0.36891025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPS	NM_004058.5	c.227C>A	p.Thr76Lys	missense_variant	Exon 3 of 5	ENST00000588776.8	NP_004049.3
CAPS	NM_080590.4	c.227C>A	p.Thr76Lys	missense_variant	Exon 3 of 5		NP_542157.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPS	ENST00000588776.8	c.227C>A	p.Thr76Lys	missense_variant	Exon 3 of 5	1	NM_004058.5	ENSP00000465883.2
ENSG00000267314	ENST00000588891.1	n.*322C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4	4		ENSP00000468419.1
ENSG00000267314	ENST00000588891.1	n.*322C>A		3_prime_UTR_variant	Exon 4 of 4	4		ENSP00000468419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460982 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726776

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	8.2
DANN	Benign	0.92
DEOGEN2	Benign	0.28	.;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.74	T
PrimateAI	Benign	0.42	T
REVEL	Uncertain	0.33
Sift4G	Uncertain	0.031	D;D;D
Vest4		0.44
MutPred		0.42		.;.;Gain of ubiquitination at T76 (P = 0.0276);
MVP		0.75
ClinPred		0.69	D
GERP RS		2.8
Varity_R		0.15

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: chr19-5914717;