CHD5 p.Ala1112Ala

Variant names:

• chr1-6130254-C-C
• NM_015557.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-6130255--
• chr1-6130255-C-A
• chr1-6130255-C-G
• chr1-6130255-C-T

Variant summary

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

The NM_015557.3(CHD5):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD5 NM_015557.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.67
• Publications: 0 publications found

Genes affected

CHD5 (HGNC:16816): (chromodomain helicase DNA binding protein 5) This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 2012]

CHD5 Gene-Disease associations (from GenCC):

• parenti-mignot neurodevelopmental syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015557.3. 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
	CHD5	NM_015557.3	MANE Select	c.		exon_region	Exon 22 of 42	NP_056372.1	Q8TDI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	ENST00000262450.8	TSL:1 MANE Select	c.		exon_region	Exon 22 of 42	ENSP00000262450.3	Q8TDI0
	CHD5	ENST00000462991.5	TSL:1	n.		exon_region	Exon 11 of 31	ENSP00000466706.1	K7EMY3
	CHD5	ENST00000496404.1	TSL:2	n.		exon_region	Exon 22 of 34	ENSP00000433676.1	F2Z2R5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-6190314;