19-47048580-C-T

Variant names:

• chr19-47048580-C-T
• rs760005587
• NM_017854.2:c.35G>A

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.35G>A​(p.Arg12His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,370,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R12L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TMEM160 NM_017854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• 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=0.23619807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.35G>A	p.Arg12His	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.35G>A	p.Arg12His	missense_variant	Exon 1 of 3	1	NM_017854.2	ENSP00000253047.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1370906 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 677782

African (AFR) AF: 0.00 AC: 0 AN: 28596

American (AMR) AF: 0.00 AC: 0 AN: 34974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24362

East Asian (EAS) AF: 0.0000303 AC: 1 AN: 33044

South Asian (SAS) AF: 0.00 AC: 0 AN: 78168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076752

Other (OTH) AF: 0.00 AC: 0 AN: 56992

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0049	T
Eigen	Benign	0.053
Eigen_PC	Benign	0.098
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.061
Sift	Benign	0.065	T
Sift4G	Benign	0.24	T
Polyphen		0.99	D
Vest4		0.28
MutPred		0.32		Loss of methylation at R12 (P = 0.0159);
MVP		0.20
MPC		2.1
ClinPred		0.79	D
GERP RS		3.4
PromoterAI		-0.26	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.097
gMVP		0.28
Mutation Taster		=90/10	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: rs760005587; hg19: chr19-47551838;