19-47048517-G-T

Variant names:

• chr19-47048517-G-T
• rs1441709400
• NM_017854.2:c.98C>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.98C>A​(p.Ala33Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000758 in 1,318,826 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. 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. A33G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: TMEM160 NM_017854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723
• 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=0.09893495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.98C>A	p.Ala33Asp	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.98C>A	p.Ala33Asp	missense_variant	Exon 1 of 3	1	NM_017854.2	ENSP00000253047.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.58e-7 AC: 1 AN: 1318826 Hom.: 0 Cov.: 32 AF XY: 0.00000154 AC XY: 1 AN XY: 649130

African (AFR) AF: 0.00 AC: 0 AN: 26070

American (AMR) AF: 0.00 AC: 0 AN: 24724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22540

East Asian (EAS) AF: 0.00 AC: 0 AN: 30022

South Asian (SAS) AF: 0.00 AC: 0 AN: 72864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3842

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051556

Other (OTH) AF: 0.0000183 AC: 1 AN: 54684

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.52
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.72
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.034
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.28	T
Polyphen		0.0090	B
Vest4		0.24
MutPred		0.21		Gain of relative solvent accessibility (P = 0.005);
MVP		0.043
MPC		1.5
ClinPred		0.12	T
GERP RS		2.1
PromoterAI		0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16
gMVP		0.55
Mutation Taster		=93/7	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: rs1441709400; hg19: chr19-47551775;