NM_003642.4:c.113-4966C>T

Variant names:

• chr2-171941742-C-T
• rs6731562
• NM_003642.4:c.113-4966C>T

Variant summary

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

The NM_003642.4(HAT1):​c.113-4966C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,952 control chromosomes in the GnomAD database, including 33,621 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 0.66 (33621 hom., cov: 31)
• Consequence: HAT1 NM_003642.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAT1	NM_003642.4	MANE Select	c.113-4966C>T		intron	N/A	NP_003633.2
	HAT1	NR_027862.2		n.153-11139C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAT1	ENST00000264108.5	TSL:1 MANE Select	c.113-4966C>T		intron	N/A	ENSP00000264108.4
	HAT1	ENST00000412731.5	TSL:1	n.113-11139C>T		intron	N/A	ENSP00000407921.1
	HAT1	ENST00000457761.6	TSL:1	n.113-4966C>T		intron	N/A	ENSP00000403466.2

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100156 AN: 151834 Hom.: 33585 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.660 AC: 100248 AN: 151952 Hom.: 33621 Cov.: 31 AF XY: 0.661 AC XY: 49079 AN XY: 74266

African (AFR) AF: 0.640 AC: 26533 AN: 41436

American (AMR) AF: 0.700 AC: 10672 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2258 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1398 AN: 5162

South Asian (SAS) AF: 0.727 AC: 3505 AN: 4824

European-Finnish (FIN) AF: 0.695 AC: 7332 AN: 10554

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46285 AN: 67936

Other (OTH) AF: 0.667 AC: 1405 AN: 2108

Alfa AF: 0.672 Hom.: 5343

Bravo AF: 0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs6731562; hg19: chr2-172798262;