4-127989722-T-C

Variant names:

• chr4-127989722-T-C
• NM_001358451.3:c.179T>C

Variant summary

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

The NM_001366038.3(ABHD18):​c.-623T>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000141 in 1,421,088 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ABHD18 NM_001366038.3 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.0001368
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51

Genes affected

ABHD18 (HGNC:26111): (abhydrolase domain containing 18) Predicted to be located in extracellular region. [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=0.0937286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD18	NM_001358451.3	c.179T>C	p.Ile60Thr	missense_variant, splice_region_variant	Exon 4 of 13	ENST00000645843.2	NP_001345380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD18	ENST00000645843.2	c.179T>C	p.Ile60Thr	missense_variant, splice_region_variant	Exon 4 of 13		NM_001358451.3	ENSP00000496010.1
ABHD18	ENST00000444616.5	c.179T>C	p.Ile60Thr	missense_variant, splice_region_variant	Exon 4 of 11	5		ENSP00000397229.1
ABHD18	ENST00000388795.10	n.177+5299T>C		intron_variant	Intron 3 of 12	5		ENSP00000373447.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1421088 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 703972

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: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.179T>C (p.I60T) alteration is located in exon 4 (coding exon 3) of the ABHD18 gene. This alteration results from a T to C substitution at nucleotide position 179, causing the isoleucine (I) at amino acid position 60 to be replaced by a threonine (T). 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	0.065
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.67
DEOGEN2	Benign	0.0016	T;.;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;D;.;D
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.094	T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	0.87	N;.;N;N
REVEL	Benign	0.11
Sift	Benign	0.55	T;.;T;T
Sift4G	Benign	0.57	T;.;T;T
Polyphen		0.0	B;.;B;.
Vest4		0.20
MutPred		0.47		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP		0.38
MPC		0.16
ClinPred		0.48	T
GERP RS		4.7
Varity_R		0.089
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-128910877;