3-197012082-C-T

Variant names:

• chr3-197012082-C-T
• rs3821716
• NM_005929.6:c.1234-1288G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MELTF	NM_005929.6	c.1234-1288G>A		intron_variant	Intron 9 of 15	ENST00000296350.10	NP_005920.2
MELTF	XM_011512850.3	c.1234-1288G>A		intron_variant	Intron 9 of 15		XP_011511152.1
MELTF	XM_006713643.4	c.1234-1288G>A		intron_variant	Intron 9 of 15		XP_006713706.2
MELTF	XM_047448150.1	c.1234-1288G>A		intron_variant	Intron 9 of 15		XP_047304106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MELTF	ENST00000296350.10	c.1234-1288G>A		intron_variant	Intron 9 of 15	1	NM_005929.6	ENSP00000296350.5
MELTF	ENST00000696016.1	c.1334-2270G>A		intron_variant	Intron 10 of 14			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

African (AFR) AF: 0.0815 AC: 3389 AN: 41564

American (AMR) AF: 0.159 AC: 2435 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3470

East Asian (EAS) AF: 0.139 AC: 722 AN: 5176

South Asian (SAS) AF: 0.0918 AC: 443 AN: 4828

European-Finnish (FIN) AF: 0.180 AC: 1904 AN: 10594

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13648 AN: 67960

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.187 Hom.: 3644

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
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3821716; hg19: chr3-196738953;