NM_017854.2:c.464T>A

Variant names:

• chr19-47046090-A-T
• NM_017854.2:c.464T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017854.2(TMEM160):​c.464T>A​(p.Leu155His) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,388,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TMEM160 NM_017854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.464T>A	p.Leu155His	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.464T>A	p.Leu155His	missense_variant	Exon 3 of 3	1	NM_017854.2	ENSP00000253047.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388050 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 686142

African (AFR) AF: 0.0000317 AC: 1 AN: 31546

American (AMR) AF: 0.00 AC: 0 AN: 36458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24958

East Asian (EAS) AF: 0.00 AC: 0 AN: 36066

South Asian (SAS) AF: 0.00 AC: 0 AN: 79634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081290

Other (OTH) AF: 0.00 AC: 0 AN: 57904

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.464T>A (p.L155H) alteration is located in exon 3 (coding exon 3) of the TMEM160 gene. This alteration results from a T to A substitution at nucleotide position 464, causing the leucine (L) at amino acid position 155 to be replaced by a histidine (H). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.8
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.32		Loss of stability (P = 0.0311);
MVP		0.92
MPC		2.5
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.74
Mutation Taster		=43/57	disease causing

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

hg19: chr19-47549348;