chr19-47046123-G-A

Variant names:

• chr19-47046123-G-A
• rs765201056
• NM_017854.2:c.431C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017854.2(TMEM160):​c.431C>T​(p.Ala144Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 1,504,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: TMEM160 NM_017854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15995893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.431C>T	p.Ala144Val	missense_variant	Exon 3 of 3	ENST00000253047.7	NP_060324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM160	ENST00000253047.7	c.431C>T	p.Ala144Val	missense_variant	Exon 3 of 3	1	NM_017854.2	ENSP00000253047.5

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151848 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: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000969 AC: 1 AN: 103244 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000444 AC: 6 AN: 1352694 Hom.: 0 Cov.: 32 AF XY: 0.00000449 AC XY: 3 AN XY: 667690

African (AFR) AF: 0.00 AC: 0 AN: 27786

American (AMR) AF: 0.00 AC: 0 AN: 32048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23660

East Asian (EAS) AF: 0.00 AC: 0 AN: 32030

South Asian (SAS) AF: 0.0000653 AC: 5 AN: 76622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065388

Other (OTH) AF: 0.0000178 AC: 1 AN: 56168

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151848 Hom.: 0 Cov.: 33 AF XY: 0.0000405 AC XY: 3 AN XY: 74164

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15248

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67920

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000271 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.431C>T (p.A144V) alteration is located in exon 3 (coding exon 3) of the TMEM160 gene. This alteration results from a C to T substitution at nucleotide position 431, causing the alanine (A) at amino acid position 144 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.2
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Benign	0.067	T
Polyphen		0.56	P
Vest4		0.085
MutPred		0.37		Gain of catalytic residue at A144 (P = 0.1896);
MVP		0.31
MPC		1.7
ClinPred		0.43	T
GERP RS		4.4
Varity_R		0.083
gMVP		0.28
Mutation Taster		=76/24	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: rs765201056; hg19: chr19-47549381;