chr14-58131719-G-A

Variant names:

• chr14-58131719-G-A
• rs45570237
• NM_001001872.4:c.1624C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001001872.4(ARMH4):​c.1624C>T​(p.Gln542*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ARMH4 NM_001001872.4 stop_gained, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001872.4. 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
	ARMH4	NM_001001872.4	MANE Select	c.1624C>T	p.Gln542*	stop_gained splice_region	Exon 4 of 8	NP_001001872.2	Q86TY3-1
	ARMH4	NM_001320173.3		c.1624C>T	p.Gln542*	stop_gained splice_region	Exon 4 of 5	NP_001307102.1	Q86TY3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMH4	ENST00000267485.7	TSL:1 MANE Select	c.1624C>T	p.Gln542*	stop_gained splice_region	Exon 4 of 8	ENSP00000267485.7	Q86TY3-1
	ARMH4	ENST00000334342.5	TSL:1	n.1789C>T		splice_region non_coding_transcript_exon	Exon 4 of 5
	ARMH4	ENST00000912025.1		c.1624C>T	p.Gln542*	stop_gained splice_region	Exon 4 of 8	ENSP00000582084.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 251026 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460112 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726380

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4616

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60254

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	33
DANN	Uncertain	0.98
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.050	N
PhyloP100		-0.40
Vest4		0.27
GERP RS		-2.4
Mutation Taster		=54/146	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs45570237; hg19: chr14-58598437;