9-5909152-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

KIAA2026 (HGNC:23378): (bromodomain containing 10)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MLANA	NM_005511.2	c.*444T>G		3_prime_UTR_variant	5/5	ENST00000381477.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLANA	ENST00000381477.8	c.*444T>G		3_prime_UTR_variant	5/5	1	NM_005511.2	P1
KIAA2026	ENST00000436015.6	c.*230+1463A>C		intron_variant, NMD_transcript_variant		3
KIAA2026	ENST00000443149.2	n.96+1463A>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.720

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.684

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

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.589

Alfa AF: 0.678 Hom.: 27163

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

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: rs1056796; hg19: chr9-5909152;