rs753538645

Variant names:

• chr19-47048605-C-A
• rs753538645
• NM_017854.2:c.10G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-47048605-C-A
• chr19-47048605-C-T

Variant summary

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

The NM_017854.2(TMEM160):​c.10G>T​(p.Gly4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000977 in 1,534,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: TMEM160 NM_017854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

TMEM160 (HGNC:26042): (transmembrane protein 160) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21471745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.10G>T	p.Gly4Cys	missense_variant	Exon 1 of 3	ENST00000253047.7	NP_060324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM160	ENST00000253047.7	c.10G>T	p.Gly4Cys	missense_variant	Exon 1 of 3	1	NM_017854.2	ENSP00000253047.5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000223 AC: 3 AN: 134736 AF XY: 0.0000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000261

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000868 AC: 12 AN: 1382518 Hom.: 0 Cov.: 32 AF XY: 0.00000877 AC XY: 6 AN XY: 684408

African (AFR) AF: 0.00 AC: 0 AN: 29148

American (AMR) AF: 0.00 AC: 0 AN: 36984

Ashkenazi Jewish (ASJ) AF: 0.000121 AC: 3 AN: 24698

East Asian (EAS) AF: 0.00 AC: 0 AN: 34014

South Asian (SAS) AF: 0.00 AC: 0 AN: 79510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4018

European-Non Finnish (NFE) AF: 0.00000647 AC: 7 AN: 1082382

Other (OTH) AF: 0.0000348 AC: 2 AN: 57464

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000890 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.10G>T (p.G4C) alteration is located in exon 1 (coding exon 1) of the TMEM160 gene. This alteration results from a G to T substitution at nucleotide position 10, causing the glycine (G) at amino acid position 4 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	0.0060	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0030	T
Eigen	Benign	0.071
Eigen_PC	Benign	0.052
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.42
MutPred		0.42		Loss of disorder (P = 0.0925);
MVP		0.20
MPC		1.4
ClinPred		0.58	D
GERP RS		1.4
PromoterAI		-0.013	Neutral
Varity_R		0.18
gMVP		0.52
Mutation Taster		=86/14	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: rs753538645; hg19: chr19-47551863;