rs935119489

Variant names:

• chr4-82429511-G-A
• rs935119489
• NM_031372.4:c.180C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-82429511-G-A
• chr4-82429511-G-C
• chr4-82429511-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_031372.4(HNRNPDL):​c.180C>T​(p.His60His) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000219 in 1,372,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: HNRNPDL NM_031372.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

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]

HNRNPDL Gene-Disease associations (from GenCC):

• autosomal dominant limb-girdle muscular dystrophy type 1G

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 4-82429511-G-A is Benign according to our data. Variant chr4-82429511-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 533026.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPDL	NM_031372.4	MANE Select	c.180C>T	p.His60His	synonymous	Exon 1 of 8	NP_112740.1
	HNRNPDL	NM_001207000.1		c.180C>T	p.His60His	synonymous	Exon 1 of 7	NP_001193929.1
	HNRNPDL	NR_003249.2		n.715C>T		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPDL	ENST00000295470.10	TSL:1 MANE Select	c.180C>T	p.His60His	synonymous	Exon 1 of 8	ENSP00000295470.5
	HNRNPDL	ENST00000621267.4	TSL:1	c.180C>T	p.His60His	synonymous	Exon 1 of 8	ENSP00000483254.1
	HNRNPDL	ENST00000614627.4	TSL:1	c.180C>T	p.His60His	synonymous	Exon 1 of 7	ENSP00000478723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1372210 Hom.: 0 Cov.: 33 AF XY: 0.00000296 AC XY: 2 AN XY: 675988

African (AFR) AF: 0.00 AC: 0 AN: 29200

American (AMR) AF: 0.00 AC: 0 AN: 31570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22894

East Asian (EAS) AF: 0.0000580 AC: 2 AN: 34490

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4916

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068298

Other (OTH) AF: 0.00 AC: 0 AN: 56532

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant limb-girdle muscular dystrophy type 1G Benign:1

Apr 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		4.2
PromoterAI		-0.20	Neutral

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: rs935119489; hg19: chr4-83350664;