6-108868900-C-G

Variant names:

• chr6-108868900-C-G
• rs372533595
• NM_032131.6:c.368C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032131.6(ARMC2):​c.368C>G​(p.Ala123Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A123V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARMC2 NM_032131.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07250589).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032131.6. 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
	ARMC2	NM_032131.6	MANE Select	c.368C>G	p.Ala123Gly	missense	Exon 4 of 18	NP_115507.4
	ARMC2	NM_001286609.2		c.-128C>G		5_prime_UTR	Exon 3 of 17	NP_001273538.1	Q8NEN0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC2	ENST00000392644.9	TSL:1 MANE Select	c.368C>G	p.Ala123Gly	missense	Exon 4 of 18	ENSP00000376417.4	Q8NEN0-1
	ARMC2	ENST00000941042.1		c.368C>G	p.Ala123Gly	missense	Exon 4 of 18	ENSP00000611101.1
	ARMC2	ENST00000896778.1		c.368C>G	p.Ala123Gly	missense	Exon 4 of 18	ENSP00000566837.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251110 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.59
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.048
Sift	Benign	0.16	T
Sift4G	Benign	0.37	T
Polyphen		0.84	P
Vest4		0.15
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.46
MPC		0.15
ClinPred		0.21	T
GERP RS		-0.036
PromoterAI		0.022	Neutral
Varity_R		0.085
gMVP		0.14
Mutation Taster		=290/10	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: rs372533595; hg19: chr6-109190103;