rs41269315

Positions:

• chr6-75253237-G-A
• chr6-75253237-G-C

Variant summary

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

The NM_018247.4(TMEM30A):​c.*2865C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,140 control chromosomes in the GnomAD database, including 234 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 0.045 (234 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: TMEM30A NM_018247.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

Genes affected

TMEM30A (HGNC:16667): (transmembrane protein 30A) Enables aminophospholipid flippase activity. Involved in several processes, including phospholipid transport; positive regulation of transport; and xenobiotic transmembrane transport. Located in endoplasmic reticulum and plasma membrane. Part of phospholipid-translocating ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM30A	NM_018247.4	c.*2865C>T		3_prime_UTR_variant	7/7	ENST00000230461.11	NP_060717.1
TMEM30A	NM_001143958.2	c.*2865C>T		3_prime_UTR_variant	6/6		NP_001137430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM30A	ENST00000230461.11	c.*2865C>T		3_prime_UTR_variant	7/7	1	NM_018247.4	ENSP00000230461.6

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6781 AN: 152014 Hom.: 234 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0422

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.0446 AC: 6781 AN: 152132 Hom.: 234 Cov.: 32 AF XY: 0.0458 AC XY: 3403 AN XY: 74376

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0420

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0512 Hom.: 57

Bravo AF: 0.0371

Asia WGS AF: 0.00635 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs41269315; hg19: chr6-75962953;