NM_018843.4:c.-113G>C

Variant names:

• chr7-87876115-C-G
• rs9655955
• NM_018843.4:c.-113G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018843.4(SLC25A40):​c.-113G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,944 control chromosomes in the GnomAD database, including 930 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (929 hom., cov: 33)
  • Exomes 𝑓: 0.065 (1 hom.)
• Consequence: SLC25A40 NM_018843.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

SLC25A40 (HGNC:29680): (solute carrier family 25 member 40) SLC25A40 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

DBF4 (HGNC:17364): (DBF4-CDC7 kinase regulatory subunit) Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A40	NM_018843.4	c.-113G>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000341119.10	NP_061331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A40	ENST00000341119.10	c.-113G>C		5_prime_UTR_variant	Exon 1 of 12	1	NM_018843.4	ENSP00000344831.5

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15128 AN: 152170 Hom.: 920 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0672

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0653 AC: 43 AN: 658 Hom.: 1 Cov.: 0 AF XY: 0.0726 AC XY: 34 AN XY: 468

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0518

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.0996 AC: 15164 AN: 152286 Hom.: 929 Cov.: 33 AF XY: 0.0992 AC XY: 7389 AN XY: 74466

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0911

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0858 Hom.: 101

Bravo AF: 0.105

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9655955; hg19: chr7-87505430;