chr10-15078577-C-G

Position:

• chr10-15078577-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001039844.3(ACBD7):​c.220G>C​(p.Ala74Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACBD7 NM_001039844.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACBD7	NM_001039844.3	c.220G>C	p.Ala74Pro	missense_variant	4/4	ENST00000356189.6
ACBD7-DCLRE1CP1	NR_144471.1	n.178+346G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACBD7	ENST00000356189.6	c.220G>C	p.Ala74Pro	missense_variant	4/4	2	NM_001039844.3	P1
ACBD7	ENST00000496890.1	n.384G>C		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Mar 31, 2024

The c.220G>C (p.A74P) alteration is located in exon 4 (coding exon 4) of the ACBD7 gene. This alteration results from a G to C substitution at nucleotide position 220, causing the alanine (A) at amino acid position 74 to be replaced by a proline (P). 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	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.025	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.56		Gain of disorder (P = 0.0865);
MVP		0.31
MPC		0.34
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.89
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1018043138; hg19: chr10-15120576;