dbSNP rs1013490726: ARMH4:p.Glu486Gln (chr14-58133255-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001872.4(ARMH4):c.1456G>C(p.Glu486Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. E486K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARMH4
NM_001001872.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARMH4 links:

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ACMG classification

Classification made for transcript

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=0.0987764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMH4	NM_001001872.4 link	c.1456G>C	p.Glu486Gln	missense_variant	Exon 3 of 8	ENST00000267485.7	NP_001001872.2	Q86TY3-1B2RUU6
ARMH4	NM_001320173.3 link	c.1456G>C	p.Glu486Gln	missense_variant	Exon 3 of 5		NP_001307102.1	Q86TY3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARMH4	ENST00000267485.7 link	c.1456G>C	p.Glu486Gln	missense_variant	Exon 3 of 8	1	NM_001001872.4	ENSP00000267485.7	Q86TY3-1
ARMH4	ENST00000334342.5 link	n.1621G>C		non_coding_transcript_exon_variant	Exon 3 of 5	1
ARMH4	ENST00000557175.5 link	n.981G>C		non_coding_transcript_exon_variant	Exon 2 of 4	3
ARMH4	ENST00000555101.1 link	c.-126G>C		upstream_gene_variant		2		ENSP00000477692.1	A0A087WT98

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.0

DANN

Benign

0.87

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.46

M_CAP

Benign

0.0080

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.1

PROVEAN

Benign

-2.3

REVEL

Benign

0.022

Sift

Benign

0.040

Sift4G

Benign

0.18

Polyphen

0.75

Vest4

0.10

MutPred

0.24

Loss of phosphorylation at T484 (P = 0.1372);

MVP

0.040

MPC

0.17

ClinPred

0.32

GERP RS

1.9

Varity_R

0.083

gMVP

0.076

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over