5-73123557-G-T

Position:

• chr5-73123557-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000454765.7(TMEM171):​c.184G>T​(p.Ala62Ser) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM171 ENST00000454765.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

Genes affected

TMEM171 (HGNC:27031): (transmembrane protein 171) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1646114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM171	NM_173490.8	c.184G>T	p.Ala62Ser	missense_variant	2/4	ENST00000454765.7	NP_775761.4
TMEM171	NM_001161342.3	c.184G>T	p.Ala62Ser	missense_variant	2/4		NP_001154814.1
TMEM171	XM_011543156.2	c.184G>T	p.Ala62Ser	missense_variant	2/4		XP_011541458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM171	ENST00000454765.7	c.184G>T	p.Ala62Ser	missense_variant	2/4	1	NM_173490.8	ENSP00000415030	P4
TMEM171	ENST00000287773.5	c.184G>T	p.Ala62Ser	missense_variant	2/4	5		ENSP00000287773	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2023

The c.184G>T (p.A62S) alteration is located in exon 2 (coding exon 1) of the TMEM171 gene. This alteration results from a G to T substitution at nucleotide position 184, causing the alanine (A) at amino acid position 62 to be replaced by a serine (S). 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	Benign	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.026
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.019	B;B
Vest4		0.20
MutPred		0.44		Gain of glycosylation at A62 (P = 0.0088);Gain of glycosylation at A62 (P = 0.0088);
MVP		0.12
MPC		0.068
ClinPred		0.084	T
GERP RS		2.4
Varity_R		0.086
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs1037377509; hg19: chr5-72419384;