NM_017854.2:c.206C>A

Variant names:

• chr19-47048409-G-T
• rs1263822268
• NM_017854.2:c.206C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017854.2(TMEM160):​c.206C>A​(p.Thr69Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,334,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. T69R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: TMEM160 NM_017854.2 missense, splice_region
• Scores: Splicing: ADA: 0.6779
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.206C>A	p.Thr69Lys	missense_variant, splice_region_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.206C>A	p.Thr69Lys	missense_variant, splice_region_variant	Exon 1 of 3	1	NM_017854.2	ENSP00000253047.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1334274 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 658410

African (AFR) AF: 0.00 AC: 0 AN: 26444

American (AMR) AF: 0.00 AC: 0 AN: 27216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22938

East Asian (EAS) AF: 0.00 AC: 0 AN: 30718

South Asian (SAS) AF: 0.00 AC: 0 AN: 74888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3886

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1060006

Other (OTH) AF: 0.00 AC: 0 AN: 55392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.31		Gain of MoRF binding (P = 0.0173);
MVP		0.36
MPC		1.4
ClinPred		0.97	D
GERP RS		4.3
PromoterAI		0.077	Neutral
Varity_R		0.62
gMVP		0.85
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.68
dbscSNV1_RF	Pathogenic	0.72
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: rs1263822268; hg19: chr19-47551667;