rs10516673

Variant names:

• chr4-82357640-T-C
• rs10516673
• NM_031370.3:c.622-196A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031370.3(HNRNPD):​c.622-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 422,184 control chromosomes in the GnomAD database, including 607 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (51 hom., cov: 33)
  • Exomes 𝑓: 0.028 (556 hom.)
• Consequence: HNRNPD NM_031370.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 2 publications found

Genes affected

HNRNPD (HGNC:5036): (heterogeneous nuclear ribonucleoprotein D) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are nucleic acid 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 repeats of quasi-RRM domains that bind to RNAs. It localizes to both the nucleus and the cytoplasm. This protein is implicated in the regulation of mRNA stability. Alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

HNRNPD Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031370.3. 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
	HNRNPD	NM_031370.3	MANE Select	c.622-196A>G		intron	N/A	NP_112738.1	Q14103-1
	HNRNPD	NM_031369.3		c.565-196A>G		intron	N/A	NP_112737.1	Q14103-2
	HNRNPD	NM_002138.4		c.622-196A>G		intron	N/A	NP_002129.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPD	ENST00000313899.12	TSL:1 MANE Select	c.622-196A>G		intron	N/A	ENSP00000313199.7	Q14103-1
	HNRNPD	ENST00000352301.8	TSL:1	c.565-196A>G		intron	N/A	ENSP00000305860.6	Q14103-2
	HNRNPD	ENST00000353341.8	TSL:1	c.622-196A>G		intron	N/A	ENSP00000313327.6	Q14103-3

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2047 AN: 152182 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00929

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0285 AC: 7684 AN: 269884 Hom.: 556 Cov.: 5 AF XY: 0.0274 AC XY: 3824 AN XY: 139626

African (AFR) AF: 0.00227 AC: 17 AN: 7504

American (AMR) AF: 0.0255 AC: 232 AN: 9092

Ashkenazi Jewish (ASJ) AF: 0.00782 AC: 73 AN: 9334

East Asian (EAS) AF: 0.212 AC: 4642 AN: 21858

South Asian (SAS) AF: 0.0166 AC: 192 AN: 11588

European-Finnish (FIN) AF: 0.0297 AC: 561 AN: 18916

Middle Eastern (MID) AF: 0.0116 AC: 15 AN: 1288

European-Non Finnish (NFE) AF: 0.00944 AC: 1638 AN: 173428

Other (OTH) AF: 0.0186 AC: 314 AN: 16876

GnomAD4 genome AF: 0.0135 AC: 2049 AN: 152300 Hom.: 51 Cov.: 33 AF XY: 0.0151 AC XY: 1125 AN XY: 74466

African (AFR) AF: 0.00257 AC: 107 AN: 41574

American (AMR) AF: 0.0220 AC: 336 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.108 AC: 562 AN: 5182

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4822

European-Finnish (FIN) AF: 0.0253 AC: 269 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00931 AC: 633 AN: 68026

Other (OTH) AF: 0.0123 AC: 26 AN: 2110

Alfa AF: 0.0101 Hom.: 5

Bravo AF: 0.0128

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.77
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10516673; hg19: chr4-83278793;