6-84126446-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014895.4(CEP162):​c.3937G>A​(p.Val1313Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,591,104 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: CEP162 NM_014895.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017172277).
• BP6: Variant 6-84126446-C-T is Benign according to our data. Variant chr6-84126446-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2517972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP162	NM_014895.4	c.3937G>A	p.Val1313Met	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>A	p.Val1313Met	missense_variant	Exon 26 of 27	5	NM_014895.4	ENSP00000385215.3

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000133 AC: 29 AN: 217780 Hom.: 0 AF XY: 0.000120 AC XY: 14 AN XY: 116910

Gnomad AFR exome AF: 0.000207

Gnomad AMR exome AF: 0.0000657

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000111

Gnomad FIN exome AF: 0.0000496

Gnomad NFE exome AF: 0.000201

Gnomad OTH exome AF: 0.000184

GnomAD4 exome AF: 0.000156 AC: 224 AN: 1438894 Hom.: 2 Cov.: 28 AF XY: 0.000160 AC XY: 114 AN XY: 714082

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.0000482

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000231

Gnomad4 SAS exome AF: 0.0000603

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.0000672

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74426

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.0000827 AC: 10

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 05, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.13
DEOGEN2	Benign	0.0034	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.51	.;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.017	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.6	.;N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.1	N;N;.
REVEL	Benign	0.038
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.19
MVP		0.030
MPC		0.016
ClinPred		0.014	T
GERP RS		1.1
Varity_R		0.018
gMVP		0.062

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;