chr3-69879137-T-A

Variant names:

• chr3-69879137-T-A
• NM_001354604.2:c.108T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001354604.2(MITF):​c.108T>A​(p.Ser36Arg) variant causes a missense 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MITF NM_001354604.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34

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 (MetaRNN=0.23057383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MITF	NM_001354604.2	c.108T>A	p.Ser36Arg	missense_variant	Exon 2 of 10	ENST00000352241.9	NP_001341533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MITF	ENST00000352241.9	c.108T>A	p.Ser36Arg	missense_variant	Exon 2 of 10	1	NM_001354604.2	ENSP00000295600.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	.;T;.;T;.;.;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	.;T;T;T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;M;M;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N;N;.;D;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D;D;.;T;D;D;D
Sift4G	Benign	0.26	T;T;.;D;D;T;T
Polyphen		0.34	B;.;B;.;P;B;.
Vest4		0.35
MutPred		0.30		Loss of phosphorylation at S36 (P = 0.0054);Loss of phosphorylation at S36 (P = 0.0054);Loss of phosphorylation at S36 (P = 0.0054);.;.;.;.;
MVP		0.38
MPC		0.75
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.45
gMVP		0.76

Splicing

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: chr3-69928288;