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. The variant received -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. 16/22 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
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03225127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014895.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP162	NM_014895.4	MANE Select	c.3937G>T	p.Val1313Leu	missense	Exon 26 of 27	NP_055710.2	Q5TB80-1
	CEP162	NM_001286206.2		c.3709G>T	p.Val1237Leu	missense	Exon 26 of 27	NP_001273135.1	Q5TB80-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP162	ENST00000403245.8	TSL:5 MANE Select	c.3937G>T	p.Val1313Leu	missense	Exon 26 of 27	ENSP00000385215.3	Q5TB80-1
	CEP162	ENST00000257766.8	TSL:1	c.3709G>T	p.Val1237Leu	missense	Exon 26 of 27	ENSP00000257766.4	Q5TB80-2
	CEP162	ENST00000962927.1		c.3937G>T	p.Val1313Leu	missense	Exon 26 of 27	ENSP00000632986.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33082

American (AMR) AF: 0.00 AC: 0 AN: 41524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25668

East Asian (EAS) AF: 0.00 AC: 0 AN: 38966

South Asian (SAS) AF: 0.00 AC: 0 AN: 82930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52254

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5726

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099256

Other (OTH) AF: 0.0000168 AC: 1 AN: 59490

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.0	N
PhyloP100		0.60
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.044
Sift	Benign	0.91	T
Sift4G	Benign	0.97	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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs577972462; hg19: chr6-84836165;