3-51975203-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001316331.2(ABHD14A-ACY1):​c.-78C>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ABHD14A-ACY1 NM_001316331.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.0003142
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD14A	NM_015407.5	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 5	ENST00000273596.8	NP_056222.2
ABHD14A-ACY1	NM_001316331.2	c.-78C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17		NP_001303260.1
ABHD14A-ACY1	NM_001316331.2	c.-78C>T		splice_region_variant	Exon 1 of 17		NP_001303260.1
ABHD14A-ACY1	NM_001316331.2	c.-78C>T		5_prime_UTR_variant	Exon 1 of 17		NP_001303260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD14A	ENST00000273596.8	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 5	1	NM_015407.5	ENSP00000273596.3
ABHD14A-ACY1	ENST00000463937.1	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 16	5		ENSP00000420487.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000321

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.74	N;D;N;.
REVEL	Benign	0.047
Sift	Uncertain	0.014	D;D;D;.
Sift4G	Uncertain	0.016	D;D;D;.
Polyphen		0.46	P;.;P;.
Vest4		0.24
MutPred		0.50		Loss of glycosylation at T24 (P = 0.0481);Loss of glycosylation at T24 (P = 0.0481);Loss of glycosylation at T24 (P = 0.0481);Loss of glycosylation at T24 (P = 0.0481);
MVP		0.53
MPC		0.17
ClinPred		0.25	T
GERP RS		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.051
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs779857203; hg19: chr3-52009219;