6-75284580-C-A

Variant names:

• chr6-75284580-C-A
• rs149782863
• NM_018247.4:c.59G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018247.4(TMEM30A):​c.59G>T​(p.Gly20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G20R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM30A NM_018247.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 0 publications found

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]

TMEM30A-DT (HGNC:48985): (TMEM30A divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17099702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018247.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM30A	NM_018247.4	MANE Select	c.59G>T	p.Gly20Val	missense	Exon 1 of 7	NP_060717.1	Q9NV96-1
	TMEM30A	NM_001143958.2		c.59G>T	p.Gly20Val	missense	Exon 1 of 6	NP_001137430.1	Q9NV96-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM30A	ENST00000230461.11	TSL:1 MANE Select	c.59G>T	p.Gly20Val	missense	Exon 1 of 7	ENSP00000230461.6	Q9NV96-1
	TMEM30A	ENST00000475111.6	TSL:1	c.59G>T	p.Gly20Val	missense	Exon 1 of 6	ENSP00000431007.1	Q9NV96-2
	TMEM30A	ENST00000873067.1		c.59G>T	p.Gly20Val	missense	Exon 1 of 7	ENSP00000543126.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250180 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461370 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726980

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111846

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.34
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.065
Sift	Uncertain	0.029	D
Sift4G	Benign	0.090	T
Polyphen		0.44	B
Vest4		0.10
MutPred		0.19		Gain of solvent accessibility (P = 0.1133)
MVP		0.71
MPC		0.86
ClinPred		0.53	D
GERP RS		4.7
PromoterAI		-0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.20
gMVP		0.57
Mutation Taster		=79/21	polymorphism

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: rs149782863; hg19: chr6-75994296;