3-197012082-C-T

Position:

• chr3-197012082-C-T

Variant summary

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

The NM_005929.6(MELTF):​c.1234-1288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,212 control chromosomes in the GnomAD database, including 2,164 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 0.16 (2164 hom., cov: 32)
• Consequence: MELTF NM_005929.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

Genes affected

MELTF (HGNC:7037): (melanotransferrin) The protein encoded by this gene is a cell-surface glycoprotein found on melanoma cells. The protein shares sequence similarity and iron-binding properties with members of the transferrin superfamily. The importance of the iron binding function has not yet been identified. This gene resides in the same region of chromosome 3 as members of the transferrin superfamily. Alternative splicing results in two transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MELTF	NM_005929.6	c.1234-1288G>A		intron_variant		ENST00000296350.10	NP_005920.2
MELTF	XM_011512850.3	c.1234-1288G>A		intron_variant			XP_011511152.1
MELTF	XM_006713643.4	c.1234-1288G>A		intron_variant			XP_006713706.2
MELTF	XM_047448150.1	c.1234-1288G>A		intron_variant			XP_047304106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MELTF	ENST00000296350.10	c.1234-1288G>A		intron_variant		1	NM_005929.6	ENSP00000296350.5
MELTF	ENST00000696016.1	c.1334-2270G>A		intron_variant				ENSP00000512332.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24210 AN: 152094 Hom.: 2162 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.159 AC: 24227 AN: 152212 Hom.: 2164 Cov.: 32 AF XY: 0.158 AC XY: 11783 AN XY: 74412

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.200

Alfa AF: 0.193 Hom.: 2979

Bravo AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.1
DANN	Benign	0.63

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: rs3821716; hg19: chr3-196738953;