chr2-171956692-G-A

Variant names:

• chr2-171956692-G-A
• rs4280427
• NM_003642.4:c.309+3691G>A

Variant summary

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

The NM_003642.4(HAT1):​c.309+3691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,782 control chromosomes in the GnomAD database, including 15,297 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 0.43 (15297 hom., cov: 33)
• Consequence: HAT1 NM_003642.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 7 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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAT1	NM_003642.4	c.309+3691G>A		intron_variant	Intron 4 of 10	ENST00000264108.5	NP_003633.2
HAT1	NR_027862.2	n.273+3691G>A		intron_variant	Intron 3 of 9
HAT1	XM_006712808.4	c.291+3691G>A		intron_variant	Intron 5 of 11		XP_006712871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAT1	ENST00000264108.5	c.309+3691G>A		intron_variant	Intron 4 of 10	1	NM_003642.4	ENSP00000264108.4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64567 AN: 151662 Hom.: 15307 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.425 AC: 64555 AN: 151782 Hom.: 15297 Cov.: 33 AF XY: 0.425 AC XY: 31545 AN XY: 74182

African (AFR) AF: 0.238 AC: 9877 AN: 41458

American (AMR) AF: 0.376 AC: 5747 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1790 AN: 3464

East Asian (EAS) AF: 0.136 AC: 705 AN: 5172

South Asian (SAS) AF: 0.550 AC: 2646 AN: 4810

European-Finnish (FIN) AF: 0.515 AC: 5400 AN: 10480

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36842 AN: 67820

Other (OTH) AF: 0.452 AC: 953 AN: 2110

Alfa AF: 0.496 Hom.: 28513

Bravo AF: 0.404

Asia WGS AF: 0.333 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.1
DANN	Benign	0.86
PhyloP100		0.47
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: rs4280427; hg19: chr2-172813218;