3-51975142-G-T

Variant names:

• chr3-51975142-G-T
• rs1483147321
• NM_015407.5:c.7G>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.-139G>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 0.0000031 in 1,290,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ABHD14A-ACY1 NM_001316331.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.163

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=0.09399775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD14A	NM_015407.5	c.7G>T	p.Gly3Trp	missense_variant	Exon 1 of 5	ENST00000273596.8	NP_056222.2
ABHD14A-ACY1	NM_001316331.2	c.-139G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17		NP_001303260.1
ABHD14A-ACY1	NM_001316331.2	c.-139G>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.7G>T	p.Gly3Trp	missense_variant	Exon 1 of 5	1	NM_015407.5	ENSP00000273596.3
ABHD14A-ACY1	ENST00000463937.1	c.7G>T	p.Gly3Trp	missense_variant	Exon 1 of 16	5		ENSP00000420487.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1138684 Hom.: 0 Cov.: 31 AF XY: 0.00000366 AC XY: 2 AN XY: 546906

Gnomad4 AFR exome AF: 0.0000430

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000373

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74316

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7G>T (p.G3W) alteration is located in exon 1 (coding exon 1) of the ABHD14A gene. This alteration results from a G to T substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0027	T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.69	T;T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.094	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.44	N;N;N;.
REVEL	Benign	0.043
Sift	Uncertain	0.0070	D;D;D;.
Sift4G	Uncertain	0.011	D;D;D;.
Polyphen		0.0	B;.;B;.
Vest4		0.35
MutPred		0.49		Loss of disorder (P = 0.005);Loss of disorder (P = 0.005);Loss of disorder (P = 0.005);Loss of disorder (P = 0.005);
MVP		0.24
MPC		0.34
ClinPred		0.23	T
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.043
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs1483147321; hg19: chr3-52009158;