6-108941704-C-T

Variant names:

• chr6-108941704-C-T
• rs911477
• NM_032131.6:c.1596+4705C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032131.6(ARMC2):​c.1596+4705C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,976 control chromosomes in the GnomAD database, including 25,826 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25826 hom., cov: 32)
• Consequence: ARMC2 NM_032131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 2 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: ClinGen, Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC2	NM_032131.6	c.1596+4705C>T		intron_variant	Intron 12 of 17	ENST00000392644.9	NP_115507.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC2	ENST00000392644.9	c.1596+4705C>T		intron_variant	Intron 12 of 17	1	NM_032131.6	ENSP00000376417.4
ARMC2	ENST00000368972.7	c.1101+4705C>T		intron_variant	Intron 11 of 16	2		ENSP00000357968.3

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87447 AN: 151858 Hom.: 25802 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.607

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.576 AC: 87511 AN: 151976 Hom.: 25826 Cov.: 32 AF XY: 0.579 AC XY: 43024 AN XY: 74260

African (AFR) AF: 0.472 AC: 19563 AN: 41426

American (AMR) AF: 0.663 AC: 10133 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3468

East Asian (EAS) AF: 0.881 AC: 4554 AN: 5168

South Asian (SAS) AF: 0.599 AC: 2892 AN: 4826

European-Finnish (FIN) AF: 0.621 AC: 6549 AN: 10538

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.584 AC: 39719 AN: 67956

Other (OTH) AF: 0.610 AC: 1284 AN: 2104

Alfa AF: 0.581 Hom.: 3208

Bravo AF: 0.583

Asia WGS AF: 0.718 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.8
DANN	Benign	0.84
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs911477; hg19: chr6-109262907;