5-73123642-A-T

Position:

• chr5-73123642-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_173490.8(TMEM171):​c.269A>T​(p.Gln90Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM171 NM_173490.8 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0490

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0310328).
• BP6: Variant 5-73123642-A-T is Benign according to our data. Variant chr5-73123642-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3178957.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM171	NM_173490.8	c.269A>T	p.Gln90Leu	missense_variant	2/4	ENST00000454765.7	NP_775761.4
TMEM171	NM_001161342.3	c.269A>T	p.Gln90Leu	missense_variant	2/4		NP_001154814.1
TMEM171	XM_011543156.2	c.269A>T	p.Gln90Leu	missense_variant	2/4		XP_011541458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM171	ENST00000454765.7	c.269A>T	p.Gln90Leu	missense_variant	2/4	1	NM_173490.8	ENSP00000415030.2
TMEM171	ENST00000287773.5	c.269A>T	p.Gln90Leu	missense_variant	2/4	5		ENSP00000287773.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.12
DANN	Benign	0.66
DEOGEN2	Benign	0.0048	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.031	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.080	N;N
REVEL	Benign	0.031
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.064
MutPred		0.33		Loss of disorder (P = 0.0197);Loss of disorder (P = 0.0197);
MVP		0.055
MPC		0.065
ClinPred		0.076	T
GERP RS		-10
Varity_R		0.037
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-72419469;