chrX-111902181-A-G

Position:

• chrX-111902181-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001195578.2(TRPC5OS):​c.332A>G​(p.Asp111Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000303 in 988,480 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000030 (0 hom. 1 hem.)
• Consequence: TRPC5OS NM_001195578.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.36

Genes affected

TRPC5OS (HGNC:40593): (TRPC5 opposite strand)

TRPC5 (HGNC:12337): (transient receptor potential cation channel subfamily C member 5) This gene belongs to the transient receptor family. It encodes one of the seven mammalian TRPC (transient receptor potential channel) proteins. The encoded protein is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na(+)-H+ exchange regulatory factor (NHERF ), interferon-induced GTP-binding protein (MX1), ring finger protein 24 (RNF24), and SEC14 domain and spectrin repeat-containing protein 1 (SESTD1). [provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07399687).
• BP6: Variant X-111902181-A-G is Benign according to our data. Variant chrX-111902181-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2248734.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC5OS	NM_001195578.2	c.332A>G	p.Asp111Gly	missense_variant	4/4	ENST00000635763.2
TRPC5	NM_012471.3	c.900+10110T>C		intron_variant		ENST00000262839.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC5OS	ENST00000635763.2	c.332A>G	p.Asp111Gly	missense_variant	4/4	2	NM_001195578.2	P1
TRPC5OS	ENST00000371970.2	c.332A>G	p.Asp111Gly	missense_variant	4/4	1		P1
TRPC5	ENST00000262839.3	c.900+10110T>C		intron_variant		1	NM_012471.3	P1
TRPC5OS	ENST00000612026.5	c.332A>G	p.Asp111Gly	missense_variant	4/4	3		P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000303 AC: 3 AN: 988480 Hom.: 0 Cov.: 25 AF XY: 0.00000329 AC XY: 1 AN XY: 304250

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000719

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

Sep 02, 2021

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	0.17
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.082	T;T;T
FATHMM_MKL	Benign	0.0074	N
MetaRNN	Benign	0.074	T;T;T
MutationAssessor	Benign	-0.34	N;N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
Polyphen		0.0	B;B;B
GERP RS		2.5
Varity_R		0.068
gMVP		0.0087

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: chrX-111145409;