NM_015407.5:c.68C>T

Variant names:

• chr3-51975203-C-T
• rs779857203
• NM_015407.5:c.68C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015407.5(ABHD14A):​c.68C>T​(p.Pro23Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000027 in 1,110,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P23R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ABHD14A NM_015407.5 missense, splice_region
• Scores: Splicing: ADA: 0.0003142
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517
• Publications: 0 publications found

Genes affected

ABHD14A (HGNC:24538): (abhydrolase domain containing 14A) Predicted to enable hydrolase activity. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ABHD14A-ACY1 (HGNC:38856): (ABHD14A-ACY1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring abhydrolase domain containing 14A (ABHD14A) and aminoacylase 1 (ACY1) genes on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the downstream gene product but its N-terminal region is distinct due to the use of an alternate start codon relative to the upstream gene. [provided by RefSeq, Oct 2015]

ABHD14B (HGNC:28235): (abhydrolase domain containing 14B) Enables hydrolase activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1020273).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015407.5. 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
	ABHD14A	NM_015407.5	MANE Select	c.68C>T	p.Pro23Leu	missense splice_region	Exon 1 of 5	NP_056222.2	Q9BUJ0
	ABHD14A-ACY1	NM_001316331.2		c.-78C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001303260.1
	ABHD14A-ACY1	NM_001316331.2		c.-78C>T		splice_region	Exon 1 of 17	NP_001303260.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD14A	ENST00000273596.8	TSL:1 MANE Select	c.68C>T	p.Pro23Leu	missense splice_region	Exon 1 of 5	ENSP00000273596.3	Q9BUJ0
	ABHD14A-ACY1	ENST00000463937.1	TSL:5	c.68C>T	p.Pro23Leu	missense splice_region	Exon 1 of 16	ENSP00000420487.1	C9JMV9
	ABHD14B	ENST00000483233.5	TSL:1	c.-298-969G>A		intron	N/A	ENSP00000420065.1	Q96IU4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000270 AC: 3 AN: 1110356 Hom.: 0 Cov.: 31 AF XY: 0.00000189 AC XY: 1 AN XY: 529068

African (AFR) AF: 0.00 AC: 0 AN: 23104

American (AMR) AF: 0.00 AC: 0 AN: 9056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14864

East Asian (EAS) AF: 0.00 AC: 0 AN: 26662

South Asian (SAS) AF: 0.00 AC: 0 AN: 30038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2988

European-Non Finnish (NFE) AF: 0.00000321 AC: 3 AN: 935466

Other (OTH) AF: 0.00 AC: 0 AN: 44710

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.52
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.047
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.016	D
Polyphen		0.46	P
Vest4		0.24
MutPred		0.50		Loss of glycosylation at T24 (P = 0.0481)
MVP		0.53
MPC		0.17
ClinPred		0.25	T
GERP RS		0.98
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.051
gMVP		0.29
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.15
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: rs779857203; hg19: chr3-52009219;