chr5-73123642-A-T

Variant names:

• chr5-73123642-A-T
• rs543295611
• NM_173490.8:c.269A>T
• TMEM171 p.Gln90Leu

Variant summary

Our verdict is

Likely benign

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q90R) has been classified 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.031).
• 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 VariationId is 3178957.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173490.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM171	NM_173490.8	MANE Select	c.269A>T	p.Gln90Leu	missense	Exon 2 of 4	NP_775761.4
	TMEM171	NM_001161342.3		c.269A>T	p.Gln90Leu	missense	Exon 2 of 4	NP_001154814.1	Q8WVE6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM171	ENST00000454765.7	TSL:1 MANE Select	c.269A>T	p.Gln90Leu	missense	Exon 2 of 4	ENSP00000415030.2	Q8WVE6-1
	TMEM171	ENST00000915846.1		c.269A>T	p.Gln90Leu	missense	Exon 1 of 3	ENSP00000585905.1
	TMEM171	ENST00000287773.5	TSL:5	c.269A>T	p.Gln90Leu	missense	Exon 2 of 4	ENSP00000287773.5	Q8WVE6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-0.049
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.037
gMVP		0.17
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs543295611;

hg19: chr5-72419469;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline