rs796296176

Variant names:

• chr16-89919342-CA-C
• rs796296176
• NM_002386.4:c.86delA

Your query was ambiguous. Multiple possible variants found:

• chr16-89919342-CA-C
• chr16-89919342-CA-CAA

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_002386.4(MC1R):​c.86delA​(p.Asn29ThrfsTer23) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MC1R NM_002386.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• Publications: 0 publications found

Genes affected

MC1R (HGNC:6929): (melanocortin 1 receptor) This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation. [provided by RefSeq, Jul 2008]

ENSG00000198211 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.91 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MC1R	NM_002386.4	c.86delA	p.Asn29ThrfsTer23	frameshift_variant	Exon 1 of 1	ENST00000555147.2	NP_002377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC1R	ENST00000555147.2	c.86delA	p.Asn29ThrfsTer23	frameshift_variant	Exon 1 of 1	6	NM_002386.4	ENSP00000451605.1
ENSG00000198211	ENST00000556922.1	c.86delA	p.Asn29ThrfsTer23	frameshift_variant	Exon 1 of 5	2		ENSP00000451560.1
MC1R	ENST00000555427.1	c.86delA	p.Asn29ThrfsTer23	frameshift_variant	Exon 3 of 4	5		ENSP00000451760.1
MC1R	ENST00000639847.1	c.86delA	p.Asn29ThrfsTer23	frameshift_variant	Exon 3 of 3	5		ENSP00000492011.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

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: rs796296176; hg19: chr16-89985750;