7-103086667-C-G

Variant names:

• chr7-103086667-C-G
• rs1241100293
• NM_031905.5:c.431C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_031905.5(ARMC10):​c.431C>G​(p.Ala144Gly) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARMC10 NM_031905.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

Genes affected

ARMC10 (HGNC:21706): (armadillo repeat containing 10) This gene encodes a protein that contains an armadillo repeat and transmembrane domain. The encoded protein decreases the transcriptional activity of the tumor suppressor protein p53 through direct interaction with the DNA-binding domain of p53, and may play a role in cell growth and survival. Upregulation of this gene may play a role in hepatocellular carcinoma. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 3. [provided by RefSeq, Sep 2011]

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 (MetaRNN=0.11262849).
• BP6: Variant 7-103086667-C-G is Benign according to our data. Variant chr7-103086667-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2472610.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC10	NM_031905.5	c.431C>G	p.Ala144Gly	missense_variant	Exon 4 of 7	ENST00000323716.8	NP_114111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC10	ENST00000323716.8	c.431C>G	p.Ala144Gly	missense_variant	Exon 4 of 7	1	NM_031905.5	ENSP00000319412.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 13, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.052
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.67
DEOGEN2	Benign	0.0048	.;.;.;.;.;T;T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.68	T;T;T;T;T;T;T;.
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	.;.;N;.;.;N;.;.
PhyloP100		2.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	1.0	N;N;N;N;N;N;N;N
REVEL	Benign	0.090
Sift	Benign	1.0	T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;B;B;B;B;B;.
Vest4		0.19
MutPred		0.75		.;.;Gain of ubiquitination at K146 (P = 0.0671);.;.;Gain of ubiquitination at K146 (P = 0.0671);.;.;
MVP		0.16
MPC		0.13
ClinPred		0.22	T
GERP RS		3.6
PromoterAI		0.0024	Neutral
Varity_R		0.056
gMVP		0.24
Mutation Taster		=83/17	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

Other links and lift over

dbSNP: rs1241100293; hg19: chr7-102727114;