3-69956130-A-G

Position:

• chr3-69956130-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354604.2(MITF):​c.956-325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,060 control chromosomes in the GnomAD database, including 33,975 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33975 hom., cov: 32)
• Consequence: MITF NM_001354604.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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]

MITF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MITF	NM_001354604.2	c.956-325A>G		intron_variant		ENST00000352241.9	NP_001341533.1
MITF	NM_000248.4	c.635-325A>G		intron_variant		ENST00000394351.9	NP_000239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MITF	ENST00000352241.9	c.956-325A>G		intron_variant		1	NM_001354604.2	ENSP00000295600.8
MITF	ENST00000394351.9	c.635-325A>G		intron_variant		1	NM_000248.4	ENSP00000377880.3

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98482 AN: 151942 Hom.: 33918 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.600

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.648 AC: 98600 AN: 152060 Hom.: 33975 Cov.: 32 AF XY: 0.644 AC XY: 47858 AN XY: 74296

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.602

Alfa AF: 0.566 Hom.: 37046

Bravo AF: 0.669

Asia WGS AF: 0.647 AC: 2252 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.33

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: rs7623610; hg19: chr3-70005281;