2-171965411-CT-TC

Variant names:

• chr2-171965411-CT-TC
• NM_003642.4:c.383_384delCTinsTC
• HAT1 p.Ser128Phe

Variant summary

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

The NM_003642.4(HAT1):​c.383_384delCTinsTC​(p.Ser128Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HAT1 NM_003642.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23
• Publications: 0 publications found

Genes affected

HAT1 (HGNC:4821): (histone acetyltransferase 1) The protein encoded by this gene is a type B histone acetyltransferase (HAT) that is involved in the rapid acetylation of newly synthesized cytoplasmic histones, which are in turn imported into the nucleus for de novo deposition onto nascent DNA chains. Histone acetylation, particularly of histone H4, plays an important role in replication-dependent chromatin assembly. Specifically, this HAT can acetylate soluble but not nucleosomal histone H4 at lysines 5 and 12, and to a lesser degree, histone H2A at lysine 5. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jun 2009]

SLC25A12 (HGNC:10982): (solute carrier family 25 member 12) This gene encodes a calcium-binding mitochondrial carrier protein. The encoded protein localizes to the mitochondria and is involved in the exchange of aspartate for glutamate across the inner mitochondrial membrane. Polymorphisms in this gene may be associated with autism, and mutations in this gene may also be a cause of global cerebral hypomyelination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]

SLC25A12 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 39

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003642.4. 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
	HAT1	NM_003642.4	MANE Select	c.383_384delCTinsTC	p.Ser128Phe	missense	N/A	NP_003633.2	O14929-1
	HAT1	NR_027862.2		n.347_348delCTinsTC		non_coding_transcript_exon	Exon 4 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAT1	ENST00000264108.5	TSL:1 MANE Select	c.383_384delCTinsTC	p.Ser128Phe	missense	N/A	ENSP00000264108.4	O14929-1
	HAT1	ENST00000412731.5	TSL:1	n.*166_*167delCTinsTC		non_coding_transcript_exon	Exon 4 of 10	ENSP00000407921.1	F8WEW1
	HAT1	ENST00000457761.6	TSL:1	n.262_263delCTinsTC		non_coding_transcript_exon	Exon 4 of 9	ENSP00000403466.2	F8W9G7

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

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: chr2-172821932;