4-82429511-G-T

Variant names:

• chr4-82429511-G-T
• NM_031372.4:c.180C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031372.4(HNRNPDL):​c.180C>A​(p.His60Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000729 in 1,372,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: HNRNPDL NM_031372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17

Genes affected

HNRNPDL (HGNC:5037): (heterogeneous nuclear ribonucleoprotein D like) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two RRM domains that bind to RNAs. Three alternatively spliced transcript variants have been described for this gene. One of the variants is probably not translated because the transcript is a candidate for nonsense-mediated mRNA decay. The protein isoforms encoded by this gene are similar to its family member HNRPD. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27010757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPDL	NM_031372.4	c.180C>A	p.His60Gln	missense_variant	Exon 1 of 8	ENST00000295470.10	NP_112740.1
HNRNPDL	NM_001207000.1	c.180C>A	p.His60Gln	missense_variant	Exon 1 of 7		NP_001193929.1
HNRNPDL	NR_003249.2	n.715C>A		non_coding_transcript_exon_variant	Exon 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPDL	ENST00000295470.10	c.180C>A	p.His60Gln	missense_variant	Exon 1 of 8	1	NM_031372.4	ENSP00000295470.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1372210 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 675988

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: 9.36e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.69	.;T;T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	0.15	N;.;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.029	D;D;D
Polyphen		0.12	B;B;.
Vest4		0.34
MutPred		0.28		Gain of glycosylation at T62 (P = 0.0163);Gain of glycosylation at T62 (P = 0.0163);Gain of glycosylation at T62 (P = 0.0163);
MVP		0.53
MPC		0.83
ClinPred		0.62	D
GERP RS		4.4
Varity_R		0.33
gMVP		0.22

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: chr4-83350664;