chr7-73865075-A-C

Variant names:

• chr7-73865075-A-C
• rs145787430
• NM_182504.4:c.155A>C

Variant summary

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

The NM_182504.4(TMEM270):​c.155A>C​(p.Gln52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,636 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q52R) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TMEM270 NM_182504.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 5 publications found

Genes affected

TMEM270 (HGNC:23018): (transmembrane protein 270) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM270	NM_182504.4	c.155A>C	p.Gln52Pro	missense_variant	Exon 2 of 3	ENST00000320531.3	NP_872310.2
TMEM270	XM_011515785.3	c.-137A>C		5_prime_UTR_variant	Exon 2 of 3		XP_011514087.1
TMEM270	XM_017011741.2	c.-137A>C		5_prime_UTR_variant	Exon 2 of 3		XP_016867230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM270	ENST00000320531.3	c.155A>C	p.Gln52Pro	missense_variant	Exon 2 of 3	1	NM_182504.4	ENSP00000316775.2
TMEM270	ENST00000426490.1	n.*95A>C		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000403621.1
TMEM270	ENST00000426490.1	n.*95A>C		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000403621.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151636 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151636 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74050

African (AFR) AF: 0.00 AC: 0 AN: 41290

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67846

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.013
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.0	T
PhyloP100		0.27
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.33		Gain of methylation at R55 (P = 0.1136);
MVP		0.19
MPC		0.073
ClinPred		0.93	D
GERP RS		2.0
Varity_R		0.83
gMVP		0.52
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145787430; hg19: chr7-73279405;