chr3-69959370-C-A

Position:

• chr3-69959370-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001354604.2(MITF):​c.1129C>A​(p.Arg377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R377R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MITF NM_001354604.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

Genes affected

MITF (HGNC:7105): (melanocyte inducing transcription factor) The protein encoded by this gene is a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. The encoded protein regulates melanocyte development and is responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the this gene cause auditory-pigmentary syndromes, such as Waardenburg syndrome type 2 and Tietz syndrome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.1).
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MITF	NM_001354604.2	c.1129C>A	p.Arg377=	synonymous_variant	9/10	ENST00000352241.9
MITF	NM_000248.4	c.808C>A	p.Arg270=	synonymous_variant	8/9	ENST00000394351.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MITF	ENST00000352241.9	c.1129C>A	p.Arg377=	synonymous_variant	9/10	1	NM_001354604.2	P4
MITF	ENST00000394351.9	c.808C>A	p.Arg270=	synonymous_variant	8/9	1	NM_000248.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.10
CADD	Benign	11
DANN	Benign	0.67

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: chr3-70008521; COSMIC: COSV100096719;