NM_005511.2:c.*444T>G

Variant names:

• chr9-5909152-T-G
• rs1056796
• NM_005511.2:c.*444T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005511.2(MLANA):​c.*444T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 159,332 control chromosomes in the GnomAD database, including 30,680 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 0.60 (28915 hom., cov: 32)
  • Exomes 𝑓: 0.68 (1765 hom.)
• Consequence: MLANA NM_005511.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 6 publications found

Genes affected

MLANA (HGNC:7124): (melan-A) Located in endoplasmic reticulum membrane; melanosome; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

BRD10 (HGNC:23378): (bromodomain containing 10)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLANA	NM_005511.2	c.*444T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000381477.8	NP_005502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLANA	ENST00000381477.8	c.*444T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_005511.2	ENSP00000370886.3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91916 AN: 151910 Hom.: 28917 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.682 AC: 4984 AN: 7304 Hom.: 1765 Cov.: 0 AF XY: 0.683 AC XY: 2679 AN XY: 3922

African (AFR) AF: 0.361 AC: 44 AN: 122

American (AMR) AF: 0.580 AC: 433 AN: 746

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 76 AN: 130

East Asian (EAS) AF: 0.586 AC: 130 AN: 222

South Asian (SAS) AF: 0.516 AC: 287 AN: 556

European-Finnish (FIN) AF: 0.720 AC: 144 AN: 200

Middle Eastern (MID) AF: 0.656 AC: 21 AN: 32

European-Non Finnish (NFE) AF: 0.730 AC: 3600 AN: 4932

Other (OTH) AF: 0.684 AC: 249 AN: 364

GnomAD4 genome AF: 0.605 AC: 91940 AN: 152028 Hom.: 28915 Cov.: 32 AF XY: 0.599 AC XY: 44475 AN XY: 74288

African (AFR) AF: 0.439 AC: 18183 AN: 41454

American (AMR) AF: 0.561 AC: 8565 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3466

East Asian (EAS) AF: 0.521 AC: 2700 AN: 5180

South Asian (SAS) AF: 0.526 AC: 2531 AN: 4816

European-Finnish (FIN) AF: 0.671 AC: 7077 AN: 10546

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48812 AN: 67978

Other (OTH) AF: 0.589 AC: 1241 AN: 2108

Alfa AF: 0.667 Hom.: 34125

Bravo AF: 0.593

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.82
PhyloP100		0.30
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: rs1056796; hg19: chr9-5909152;