chr19-47046237-C-T

Variant names:

• chr19-47046237-C-T
• NM_017854.2:c.317G>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.317G>A​(p.Gly106Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM160 NM_017854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50
• 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, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.317G>A	p.Gly106Asp	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.317G>A	p.Gly106Asp	missense_variant	Exon 3 of 3	1	NM_017854.2	ENSP00000253047.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384464 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 683542

African (AFR) AF: 0.00 AC: 0 AN: 31534

American (AMR) AF: 0.00 AC: 0 AN: 35252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25024

East Asian (EAS) AF: 0.00 AC: 0 AN: 35850

South Asian (SAS) AF: 0.00 AC: 0 AN: 79058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4096

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078794

Other (OTH) AF: 0.00 AC: 0 AN: 57696

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317G>A (p.G106D) alteration is located in exon 3 (coding exon 3) of the TMEM160 gene. This alteration results from a G to A substitution at nucleotide position 317, causing the glycine (G) at amino acid position 106 to be replaced by an aspartic acid (D). 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	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.53		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.76
MPC		2.3
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.94
gMVP		0.94
Mutation Taster		=47/53	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: chr19-47549495;