chr7-73865083-C-T

Variant names:

• chr7-73865083-C-T
• rs118088869
• NM_182504.4:c.163C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_182504.4(TMEM270):​c.163C>T​(p.Arg55Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,553,032 control chromosomes in the GnomAD database, including 727 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. R55P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.023 (56 hom., cov: 33)
  • Exomes 𝑓: 0.028 (671 hom.)
• Consequence: TMEM270 NM_182504.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004664302).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3459/151662) while in subpopulation NFE AF = 0.0309 (2092/67808). AF 95% confidence interval is 0.0297. There are 56 homozygotes in GnomAd4. There are 1682 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182504.4. 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
	TMEM270	NM_182504.4	MANE Select	c.163C>T	p.Arg55Trp	missense	Exon 2 of 3	NP_872310.2	Q6UE05-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM270	ENST00000320531.3	TSL:1 MANE Select	c.163C>T	p.Arg55Trp	missense	Exon 2 of 3	ENSP00000316775.2	Q6UE05-1
	TMEM270	ENST00000426490.1	TSL:5	n.*103C>T		non_coding_transcript_exon	Exon 3 of 4	ENSP00000403621.1	Q6UE05-2
	TMEM270	ENST00000426490.1	TSL:5	n.*103C>T		3_prime_UTR	Exon 3 of 4	ENSP00000403621.1	Q6UE05-2

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3462 AN: 151538 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.00943

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0370

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.0111

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0274

GnomAD2 exomes AF: 0.0249 AC: 5173 AN: 207600 AF XY: 0.0258

Gnomad AFR exome AF: 0.00891

Gnomad AMR exome AF: 0.0168

Gnomad ASJ exome AF: 0.0347

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0455

Gnomad NFE exome AF: 0.0313

Gnomad OTH exome AF: 0.0279

GnomAD4 exome AF: 0.0284 AC: 39807 AN: 1401370 Hom.: 671 Cov.: 35 AF XY: 0.0284 AC XY: 19592 AN XY: 690746

African (AFR) AF: 0.00927 AC: 292 AN: 31508

American (AMR) AF: 0.0176 AC: 630 AN: 35854

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 801 AN: 22356

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38836

South Asian (SAS) AF: 0.0147 AC: 1128 AN: 76502

European-Finnish (FIN) AF: 0.0479 AC: 2463 AN: 51462

Middle Eastern (MID) AF: 0.0295 AC: 162 AN: 5494

European-Non Finnish (NFE) AF: 0.0303 AC: 32774 AN: 1081712

Other (OTH) AF: 0.0270 AC: 1556 AN: 57646

GnomAD4 genome AF: 0.0228 AC: 3459 AN: 151662 Hom.: 56 Cov.: 33 AF XY: 0.0227 AC XY: 1682 AN XY: 74134

African (AFR) AF: 0.00943 AC: 390 AN: 41376

American (AMR) AF: 0.0165 AC: 252 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 128 AN: 3464

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5066

South Asian (SAS) AF: 0.0111 AC: 53 AN: 4796

European-Finnish (FIN) AF: 0.0445 AC: 471 AN: 10582

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0309 AC: 2092 AN: 67808

Other (OTH) AF: 0.0266 AC: 56 AN: 2104

Alfa AF: 0.0266 Hom.: 108

Bravo AF: 0.0204

TwinsUK AF: 0.0245 AC: 91

ALSPAC AF: 0.0309 AC: 119

ESP6500AA AF: 0.00863 AC: 32

ESP6500EA AF: 0.0322 AC: 264

ExAC AF: 0.0244 AC: 2942

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.8
DANN	Benign	0.94
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.46
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.014
Sift	Benign	0.13	T
Sift4G	Benign	0.077	T
Polyphen		0.027	B
Vest4		0.031
MPC		0.021
ClinPred		0.012	T
GERP RS		1.4
Varity_R		0.063
gMVP		0.066
Mutation Taster		=98/2	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: rs118088869; hg19: chr7-73279413; COSMIC: COSV99067313;