chr2-177212837-A-C

Variant names:

• chr2-177212837-A-C
• rs1688739725
• NM_194247.4:c.38A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194247.4(HNRNPA3):​c.38A>C​(p.Asp13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HNRNPA3 NM_194247.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16
• Publications: 0 publications found

Genes affected

HNRNPA3 (HGNC:24941): (heterogeneous nuclear ribonucleoprotein A3) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000229337 (HGNC:):

MIR4444-1 (HGNC:41710): (microRNA 4444-1) 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22316435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194247.4. 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
	HNRNPA3	NM_194247.4	MANE Select	c.38A>C	p.Asp13Ala	missense	Exon 1 of 11	NP_919223.1	P51991-1
	HNRNPA3	NM_001330249.2		c.38A>C	p.Asp13Ala	missense	Exon 1 of 11	NP_001317178.1	P51991-1
	HNRNPA3	NM_001330250.2		c.38A>C	p.Asp13Ala	missense	Exon 1 of 10	NP_001317179.1	A0A7I2V2R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA3	ENST00000392524.7	TSL:5 MANE Select	c.38A>C	p.Asp13Ala	missense	Exon 1 of 11	ENSP00000376309.2	P51991-1
	HNRNPA3	ENST00000435711.5	TSL:1	c.38A>C	p.Asp13Ala	missense	Exon 1 of 10	ENSP00000416340.1	P51991-1
	HNRNPA3	ENST00000678111.1		c.38A>C	p.Asp13Ala	missense	Exon 1 of 11	ENSP00000504135.1	P51991-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.17
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	26
DANN	Benign	0.94
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.30	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.52	N
REVEL	Benign	0.24
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.12	T
Polyphen		0.015	B
Vest4		0.15
MutPred		0.26		Gain of MoRF binding (P = 0.0545)
MVP		0.77
MPC		2.0
ClinPred		0.59	D
GERP RS		5.0
PromoterAI		-0.092	Neutral
Varity_R		0.23
gMVP		0.73
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1688739725; hg19: chr2-178077565;