19-19051821-A-G

Variant names:

• chr19-19051821-A-G
• rs369157884
• NM_001199196.2:c.479A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001199196.2(ARMC6):​c.479A>G​(p.Asn160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,613,930 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000052 (1 hom.)
• Consequence: ARMC6 NM_001199196.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.247
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04376164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199196.2. 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
	ARMC6	NM_001199196.2	MANE Select	c.479A>G	p.Asn160Ser	missense	Exon 5 of 9	NP_001186125.1	Q6NXE6-1
	ARMC6	NM_001439252.1		c.479A>G	p.Asn160Ser	missense	Exon 5 of 9	NP_001426181.1
	ARMC6	NM_001439253.1		c.404A>G	p.Asn135Ser	missense	Exon 4 of 8	NP_001426182.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC6	ENST00000535612.6	TSL:1 MANE Select	c.479A>G	p.Asn160Ser	missense	Exon 5 of 9	ENSP00000444156.1	Q6NXE6-1
	ARMC6	ENST00000392335.6	TSL:1	c.404A>G	p.Asn135Ser	missense	Exon 4 of 8	ENSP00000376147.2	Q6NXE6-2
	ARMC6	ENST00000392336.7	TSL:2	c.479A>G	p.Asn160Ser	missense	Exon 4 of 8	ENSP00000376148.3	Q6NXE6-1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 251016 AF XY: 0.000147

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000520 AC: 76 AN: 1461760 Hom.: 1 Cov.: 31 AF XY: 0.0000701 AC XY: 51 AN XY: 727168

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111984

Other (OTH) AF: 0.0000662 AC: 4 AN: 60392

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74330

African (AFR) AF: 0.0000724 AC: 3 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000823 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.49
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.25
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.018
Sift	Benign	0.49	T
Sift4G	Benign	0.42	T
Polyphen		0.0080	B
Vest4		0.11
MVP		0.28
MPC		0.18
ClinPred		0.0045	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.018
gMVP		0.039
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369157884; hg19: chr19-19162630;