5-93620998-C-T

Variant names:

• chr5-93620998-C-T
• NM_032042.6:c.1240G>A

Variant summary

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

The NM_032042.6(ARB2A):​c.1240G>A​(p.Glu414Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E414Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARB2A NM_032042.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.32

Genes affected

ARB2A (HGNC:25365): (ARB2 cotranscriptional regulator A) Predicted to contribute to siRNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA; neural crest cell development; and regulation of alternative mRNA splicing, via spliceosome. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

MIR2277 (HGNC:37314): (microRNA 2277) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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=0.19299582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARB2A	NM_032042.6	c.1240G>A	p.Glu414Lys	missense_variant	Exon 11 of 11	ENST00000395965.8	NP_114431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM172A	ENST00000395965.8	c.1240G>A	p.Glu414Lys	missense_variant	Exon 11 of 11	1	NM_032042.6	ENSP00000379294.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458504 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725610

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;.;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.66	N;N;N;N
REVEL	Benign	0.054
Sift	Uncertain	0.010	D;D;D;D
Sift4G	Benign	0.061	T;T;T;D
Polyphen		0.31	B;.;P;.
Vest4		0.27
MutPred		0.28		Gain of MoRF binding (P = 0.02);.;.;.;
MVP		0.56
MPC		1.1
ClinPred		0.81	D
GERP RS		3.2
Varity_R		0.32
gMVP		0.54

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: chr5-92956704;