10-15078970-T-C

Position:

• chr10-15078970-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039844.3(ACBD7):​c.83A>G​(p.Glu28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ACBD7 NM_001039844.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

Genes affected

ACBD7 (HGNC:17715): (acyl-CoA binding domain containing 7) Predicted to enable fatty-acyl-CoA binding activity and lipid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACBD7-DCLRE1CP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35534894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACBD7	NM_001039844.3	c.83A>G	p.Glu28Gly	missense_variant	2/4	ENST00000356189.6
ACBD7-DCLRE1CP1	NR_144471.1	n.131A>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACBD7	ENST00000356189.6	c.83A>G	p.Glu28Gly	missense_variant	2/4	2	NM_001039844.3	P1
ACBD7	ENST00000496890.1	n.247A>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456236 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724498

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: 9.02e-7

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.83A>G (p.E28G) alteration is located in exon 2 (coding exon 2) of the ACBD7 gene. This alteration results from a A to G substitution at nucleotide position 83, causing the glutamic acid (E) at amino acid position 28 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.13
Sift	Uncertain	0.015	D
Sift4G	Benign	0.16	T
Polyphen		0.93	P
Vest4		0.34
MutPred		0.40		Gain of ubiquitination at K27 (P = 0.0798);
MVP		0.24
MPC		0.13
ClinPred		0.89	D
GERP RS		1.5
Varity_R		0.65
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-15120969;