rs555727065

Variant names:

• chr3-51975164-T-G
• rs555727065
• NM_015407.5:c.29T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015407.5(ABHD14A):​c.29T>G​(p.Phe10Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,284,936 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ABHD14A NM_015407.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.666
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04799652).

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.29T>G	p.Phe10Cys	missense	Exon 1 of 5	NP_056222.2	Q9BUJ0
	ABHD14A-ACY1	NM_001316331.2		c.-117T>G		5_prime_UTR	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.29T>G	p.Phe10Cys	missense	Exon 1 of 5	ENSP00000273596.3	Q9BUJ0
	ABHD14A-ACY1	ENST00000463937.1	TSL:5	c.29T>G	p.Phe10Cys	missense	Exon 1 of 16	ENSP00000420487.1	C9JMV9
	ABHD14B	ENST00000483233.5	TSL:1	c.-298-930A>C		intron	N/A	ENSP00000420065.1	Q96IU4-1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152030 Hom.: 1 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: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 6874 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 24 AN: 1132794 Hom.: 0 Cov.: 31 AF XY: 0.0000258 AC XY: 14 AN XY: 543404

African (AFR) AF: 0.00 AC: 0 AN: 23232

American (AMR) AF: 0.00 AC: 0 AN: 9610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15426

East Asian (EAS) AF: 0.00 AC: 0 AN: 26878

South Asian (SAS) AF: 0.000524 AC: 19 AN: 36226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3072

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 947792

Other (OTH) AF: 0.000110 AC: 5 AN: 45528

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152142 Hom.: 1 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000237 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.0018	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.67
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.36
MutPred		0.28		Gain of helix (P = 0.132)
MVP		0.59
MPC		0.37
ClinPred		0.54	D
GERP RS		2.7
PromoterAI		-0.22	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.23
gMVP		0.31
Mutation Taster		=95/5	polymorphism

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: rs555727065; hg19: chr3-52009180;