10-15078600-A-G

Position:

• chr10-15078600-A-G

Variant summary

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

The NM_001039844.3(ACBD7):​c.197T>C​(p.Leu66Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 6.8e-7 (0 hom.)
• Consequence: ACBD7 NM_001039844.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21655732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACBD7	NM_001039844.3	c.197T>C	p.Leu66Ser	missense_variant	4/4	ENST00000356189.6
ACBD7-DCLRE1CP1	NR_144471.1	n.178+323T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACBD7	ENST00000356189.6	c.197T>C	p.Leu66Ser	missense_variant	4/4	2	NM_001039844.3	P1
ACBD7	ENST00000496890.1	n.361T>C		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

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: 0.00

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

Nov 07, 2022

The c.197T>C (p.L66S) alteration is located in exon 4 (coding exon 4) of the ACBD7 gene. This alteration results from a T to C substitution at nucleotide position 197, causing the leucine (L) at amino acid position 66 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.95	D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Benign	0.043	D
Sift4G	Uncertain	0.031	D
Polyphen		0.44	B
Vest4		0.38
MutPred		0.57		Gain of disorder (P = 0.0091);
MVP		0.31
MPC		0.18
ClinPred		0.95	D
GERP RS		4.9
Varity_R		0.34
gMVP		0.62

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: rs1844710833; hg19: chr10-15120599;