19-19051693-C-G

Position:

• chr19-19051693-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199196.2(ARMC6):​c.351C>G​(p.Phe117Leu) 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. 12/21 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)
• Consequence: ARMC6 NM_001199196.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.460

Genes affected

ARMC6 (HGNC:25049): (armadillo repeat containing 6) The function of this gene's protein product has not been determined. A related protein in mouse suggests that this protein has a conserved function. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20639595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC6	NM_001199196.2	c.351C>G	p.Phe117Leu	missense_variant	5/9	ENST00000535612.6	NP_001186125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC6	ENST00000535612.6	c.351C>G	p.Phe117Leu	missense_variant	5/9	1	NM_001199196.2	ENSP00000444156.1

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

Jan 03, 2024

The c.351C>G (p.F117L) alteration is located in exon 5 (coding exon 4) of the ARMC6 gene. This alteration results from a C to G substitution at nucleotide position 351, causing the phenylalanine (F) at amino acid position 117 to be replaced by a leucine (L). 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	Pathogenic	0.80
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	.;T;T;T;.;T;T;T;T;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.72	.;.;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	.;L;.;.;.;.;.;.;.;.;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.84	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.37	T;T;D;T;T;T;D;D;D;D;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;D;T;T
Polyphen		0.81	.;P;.;.;.;.;.;.;.;.;P
Vest4		0.36
MutPred		0.52		.;Loss of ubiquitination at K122 (P = 0.1351);.;Loss of ubiquitination at K122 (P = 0.1351);.;.;.;.;.;.;Loss of ubiquitination at K122 (P = 0.1351);
MVP		0.26
MPC		0.28
ClinPred		0.21	T
GERP RS		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.38

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: chr19-19162502;