chr19-47046183-A-G

Variant names:

• chr19-47046183-A-G
• NM_017854.2:c.371T>C

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.371T>C​(p.Leu124Pro) variant causes a missense change. 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: 5.41
• 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, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2	c.371T>C	p.Leu124Pro	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.371T>C	p.Leu124Pro	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: 1360928 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 672328

African (AFR) AF: 0.00 AC: 0 AN: 29602

American (AMR) AF: 0.00 AC: 0 AN: 30802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24074

East Asian (EAS) AF: 0.00 AC: 0 AN: 33578

South Asian (SAS) AF: 0.00 AC: 0 AN: 77306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4180

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070162

Other (OTH) AF: 0.00 AC: 0 AN: 56582

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.371T>C (p.L124P) alteration is located in exon 3 (coding exon 3) of the TMEM160 gene. This alteration results from a T to C substitution at nucleotide position 371, causing the leucine (L) at amino acid position 124 to be replaced by a proline (P). 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	0.91
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.97	L
PhyloP100		5.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.59		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.89
MPC		2.7
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.91
gMVP		0.93
Mutation Taster		=41/59	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: chr19-47549441;