chr6-108868959-G-A

Position:

• chr6-108868959-G-A

Variant summary

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

The NM_032131.6(ARMC2):​c.427G>A​(p.Ala143Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARMC2 NM_032131.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.215

Genes affected

ARMC2 (HGNC:23045): (armadillo repeat containing 2) Involved in sperm axoneme assembly. Implicated in spermatogenic failure 38. [provided by Alliance of Genome Resources, Apr 2022]

ARMC2 (HGNC:):

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=0.02307269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC2	NM_032131.6	c.427G>A	p.Ala143Thr	missense_variant	4/18	ENST00000392644.9	NP_115507.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC2	ENST00000392644.9	c.427G>A	p.Ala143Thr	missense_variant	4/18	1	NM_032131.6	ENSP00000376417.4
ARMC2	ENST00000237512.4	c.427G>A	p.Ala143Thr	missense_variant	4/5	2		ENSP00000237512.4
ARMC2	ENST00000368972	c.-69G>A		5_prime_UTR_variant	3/17	2		ENSP00000357968.3
ARMC2	ENST00000414610.1	c.-21G>A		upstream_gene_variant		5		ENSP00000393191.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 24, 2024

The c.427G>A (p.A143T) alteration is located in exon 4 (coding exon 3) of the ARMC2 gene. This alteration results from a G to A substitution at nucleotide position 427, causing the alanine (A) at amino acid position 143 to be replaced by a threonine (T). 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	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.6
DANN	Benign	0.88
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.023	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.019
Sift	Benign	0.68	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;.
Vest4		0.078
MutPred		0.14		Gain of phosphorylation at A143 (P = 0.0409);Gain of phosphorylation at A143 (P = 0.0409);
MVP		0.17
MPC		0.12
ClinPred		0.013	T
GERP RS		-2.5
Varity_R		0.030
gMVP		0.13

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: chr6-109190162;