rs577972462

Variant names:

• chr6-84126446-C-A
• rs577972462
• NM_014895.4:c.3937G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-84126446-C-A
• chr6-84126446-C-T

Variant summary

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

The NM_014895.4(CEP162):​c.3937G>T​(p.Val1313Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,438,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1313M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CEP162 NM_014895.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596

Genes affected

CEP162 (HGNC:21107): (centrosomal protein 162) Involved in cilium assembly. Located in axonemal microtubule; centriole; and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

MRAP2 (HGNC:21232): (melanocortin 2 receptor accessory protein 2) This gene encodes a protein that modulates melanocortin receptor signaling. The encoded protein has been shown to interact with all known melanocortin receptors and may regulate both receptor trafficking and activation in response to ligands. Mice lacking a functional copy of this gene exhibit severe obesity and a mutation in this gene may be associated with severe obesity in human patients. [provided by RefSeq, Oct 2016]

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 (MetaRNN=0.03225127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP162	NM_014895.4	c.3937G>T	p.Val1313Leu	missense_variant	Exon 26 of 27	ENST00000403245.8	NP_055710.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP162	ENST00000403245.8	c.3937G>T	p.Val1313Leu	missense_variant	Exon 26 of 27	5	NM_014895.4	ENSP00000385215.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1438896 Hom.: 0 Cov.: 28 AF XY: 0.00000280 AC XY: 2 AN XY: 714082

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: 9.10e-7

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.1
DANN	Benign	0.65
DEOGEN2	Benign	0.0035	.;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.59	.;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.0	.;N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.48	N;N;.
REVEL	Benign	0.044
Sift	Benign	0.91	T;T;.
Sift4G	Benign	0.97	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.18
MutPred		0.15		.;Loss of methylation at K1318 (P = 0.0693);.;
MVP		0.030
MPC		0.016
ClinPred		0.048	T
GERP RS		1.1
Varity_R		0.032
gMVP		0.073

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: rs577972462; hg19: chr6-84836165;