6-35748827-C-A

Position:

• chr6-35748827-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286574.2(ARMC12):​c.980C>A​(p.Ser327Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ARMC12 NM_001286574.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33

Genes affected

ARMC12 (HGNC:21099): (armadillo repeat containing 12) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3345989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC12	NM_001286574.2	c.980C>A	p.Ser327Tyr	missense_variant	6/6	ENST00000373866.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC12	ENST00000373866.4	c.980C>A	p.Ser327Tyr	missense_variant	6/6	3	NM_001286574.2	A1
ARMC12	ENST00000288065.6	c.1061C>A	p.Ser354Tyr	missense_variant	6/6	1		P3
ARMC12	ENST00000373869.7	c.950C>A	p.Ser317Tyr	missense_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461594 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727086

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Apr 26, 2024

The c.1061C>A (p.S354Y) alteration is located in exon 6 (coding exon 6) of the ARMC12 gene. This alteration results from a C to A substitution at nucleotide position 1061, causing the serine (S) at amino acid position 354 to be replaced by a tyrosine (Y). 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	0.097
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	.;.;T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	.;.;M
MutationTaster	Benign	0.75	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.66	N;N;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.52
MutPred		0.44		.;Loss of disorder (P = 0.0202);.;
MVP		0.52
MPC		0.43
ClinPred		0.67	D
GERP RS		4.1
Varity_R		0.23
gMVP		0.28

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: chr6-35716604;