NM_001354604.2:c.104+24163C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001354604.2(MITF):c.104+24163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000727 in 1,375,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

MITF
NM_001354604.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.476

Publications

1 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

Tietz syndrome
Inheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet
Waardenburg syndrome type 2
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Waardenburg syndrome type 2A
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
melanoma, cutaneous malignant, susceptibility to, 8
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
renal cell carcinoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
Waardenburg syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
Waardenburg-Shah syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MITF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06525633).

BP6

Variant 3-69763864-C-T is Benign according to our data. Variant chr3-69763864-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653963.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354604.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MITF	NM_001354604.2	MANE Select	c.104+24163C>T		intron	N/A	NP_001341533.1	O75030-1
MITF	NM_006722.3		c.23C>T	p.Ser8Leu	missense	Exon 1 of 10	NP_006713.1	O75030-6
MITF	NM_001354605.2		c.104+24163C>T		intron	N/A	NP_001341534.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MITF	ENST00000352241.9	TSL:1 MANE Select	c.104+24163C>T		intron	N/A	ENSP00000295600.8	O75030-1
MITF	ENST00000448226.9	TSL:5	c.23C>T	p.Ser8Leu	missense	Exon 1 of 10	ENSP00000391803.3	O75030-6
MITF	ENST00000956046.1		c.104+24163C>T		intron	N/A	ENSP00000626105.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000537

AC:

AN:

186150

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000360

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000654

AC:

AN:

1222814

Hom.:

Cov.:

AF XY:

0.00000333

AC XY:

AN XY:

599916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27608

American (AMR)

AF:

0.0000306

AC:

AN:

32658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19440

East Asian (EAS)

AF:

0.00

AC:

AN:

23290

South Asian (SAS)

AF:

0.00

AC:

AN:

77992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4728

European-Non Finnish (NFE)

AF:

0.00000625

AC:

AN:

960634

Other (OTH)

AF:

0.0000214

AC:

AN:

46640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.0

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.30

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.54

M_CAP

Benign

0.0065

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

PhyloP100

-0.48

PROVEAN

Benign

-1.3

REVEL

Benign

0.011

Sift

Uncertain

0.0090

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.18

MutPred

0.34

Loss of loop (P = 0.0374)

MVP

0.17

ClinPred

0.049

GERP RS

-3.2

PromoterAI

-0.0099

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over