chr17-8295368-C-T

Variant names:

• chr17-8295368-C-T
• rs1861956
• NM_001320870.2:c.-561G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320870.2(SLC25A35):​c.-561G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 985,354 control chromosomes in the GnomAD database, including 64,576 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 0.32 (7740 hom., cov: 32)
  • Exomes 𝑓: 0.37 (56836 hom.)
• Consequence: SLC25A35 NM_001320870.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 2 publications found

Genes affected

SLC25A35 (HGNC:31921): (solute carrier family 25 member 35) SLC25A35 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320870.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A35	NM_001320870.2	MANE Select	c.-561G>A		5_prime_UTR	Exon 1 of 5	NP_001307799.1	Q3KQZ1-1
	SLC25A35	NM_001320871.2		c.-561G>A		5_prime_UTR	Exon 1 of 7	NP_001307800.1	Q3KQZ1-4
	SLC25A35	NM_001320872.2		c.-561G>A		5_prime_UTR	Exon 1 of 7	NP_001307801.1	Q3KQZ1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A35	ENST00000577745.2	TSL:1 MANE Select	c.-561G>A		5_prime_UTR	Exon 1 of 5	ENSP00000464231.1	Q3KQZ1-1
	SLC25A35	ENST00000879454.1		c.-561G>A		5_prime_UTR	Exon 1 of 4	ENSP00000549513.1
	SLC25A35	ENST00000939396.1		c.-561G>A		5_prime_UTR	Exon 1 of 4	ENSP00000609455.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47965 AN: 151916 Hom.: 7729 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.369 AC: 307087 AN: 833320 Hom.: 56836 Cov.: 31 AF XY: 0.369 AC XY: 142189 AN XY: 384886

African (AFR) AF: 0.272 AC: 4297 AN: 15796

American (AMR) AF: 0.254 AC: 250 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1708 AN: 5156

East Asian (EAS) AF: 0.131 AC: 478 AN: 3638

South Asian (SAS) AF: 0.322 AC: 5310 AN: 16478

European-Finnish (FIN) AF: 0.288 AC: 80 AN: 278

Middle Eastern (MID) AF: 0.339 AC: 550 AN: 1624

European-Non Finnish (NFE) AF: 0.374 AC: 285261 AN: 762058

Other (OTH) AF: 0.335 AC: 9153 AN: 27306

GnomAD4 genome AF: 0.316 AC: 48003 AN: 152034 Hom.: 7740 Cov.: 32 AF XY: 0.309 AC XY: 22965 AN XY: 74326

African (AFR) AF: 0.279 AC: 11584 AN: 41498

American (AMR) AF: 0.282 AC: 4311 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3464

East Asian (EAS) AF: 0.130 AC: 672 AN: 5152

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4808

European-Finnish (FIN) AF: 0.258 AC: 2733 AN: 10590

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24865 AN: 67930

Other (OTH) AF: 0.319 AC: 673 AN: 2108

Alfa AF: 0.341 Hom.: 1972

Bravo AF: 0.317

Asia WGS AF: 0.278 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.9
DANN	Benign	0.88
PhyloP100		1.3
PromoterAI		0.0018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1861956; hg19: chr17-8198686; COSMIC: COSV66295038;