chr14-58138399-C-G

Position:

• chr14-58138399-C-G

Variant summary

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

The NM_001001872.4(ARMH4):​c.960G>C​(p.Glu320Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ARMH4 NM_001001872.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.170

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

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=0.075633466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMH4	NM_001001872.4	c.960G>C	p.Glu320Asp	missense_variant	2/8	ENST00000267485.7
ARMH4	NM_001320173.3	c.960G>C	p.Glu320Asp	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMH4	ENST00000267485.7	c.960G>C	p.Glu320Asp	missense_variant	2/8	1	NM_001001872.4	P1
ARMH4	ENST00000334342.5	n.1125G>C		non_coding_transcript_exon_variant	2/5	1
ARMH4	ENST00000557175.5	n.843G>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33

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 Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

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

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

Jul 06, 2021

The c.960G>C (p.E320D) alteration is located in exon 2 (coding exon 1) of the C14orf37 gene. This alteration results from a G to C substitution at nucleotide position 960, causing the glutamic acid (E) at amino acid position 320 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.034
Sift	Benign	0.34	T
Sift4G	Benign	0.27	T
Polyphen		0.79	P
Vest4		0.098
MutPred		0.20		Loss of methylation at K318 (P = 0.1372);
MVP		0.040
MPC		0.078
ClinPred		0.31	T
GERP RS		1.6
Varity_R		0.048
gMVP		0.052

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

LitVar

Other links and lift over

dbSNP: rs1566599464; hg19: chr14-58605117;