rs771745123

Variant names:

• chr10-68527284-C-A
• rs771745123
• NM_152707.4:c.92G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-68527284-C-A
• chr10-68527284-C-G
• chr10-68527284-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP2 PP5 BP4

The NM_152707.4(SLC25A16):​c.92G>T​(p.Arg31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,395,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SLC25A16 NM_152707.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:2 U:1
• Conservation: PhyloP100: 1.99
• Publications: 2 publications found

Genes affected

SLC25A16 (HGNC:10986): (solute carrier family 25 member 16) This gene encodes a protein that contains three tandemly repeated mitochondrial carrier protein domains. The encoded protein is localized in the inner membrane and facilitates the rapid transport and exchange of molecules between the cytosol and the mitochondrial matrix space. This gene has a possible role in Graves' disease. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.57984 (below the threshold of 3.09). Trascript score misZ: -0.19574 (below the threshold of 3.09).
• PP5: Variant 10-68527284-C-A is Pathogenic according to our data. Variant chr10-68527284-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 545498.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
• BP4: Computational evidence support a benign effect (MetaRNN=0.27472842). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A16	NM_152707.4	c.92G>T	p.Arg31Leu	missense_variant	Exon 1 of 9	ENST00000609923.6	NP_689920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A16	ENST00000609923.6	c.92G>T	p.Arg31Leu	missense_variant	Exon 1 of 9	1	NM_152707.4	ENSP00000476815.1
SLC25A16	ENST00000493963.5	n.92G>T		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000476283.1
SLC25A16	ENST00000491102.2	n.92G>T		non_coding_transcript_exon_variant	Exon 1 of 4	4		ENSP00000476555.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000676 AC: 1 AN: 147956 AF XY: 0.0000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000100 AC: 14 AN: 1395900 Hom.: 0 Cov.: 31 AF XY: 0.0000174 AC XY: 12 AN XY: 688700

African (AFR) AF: 0.00 AC: 0 AN: 30888

American (AMR) AF: 0.00 AC: 0 AN: 35588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25000

East Asian (EAS) AF: 0.00 AC: 0 AN: 35266

South Asian (SAS) AF: 0.000139 AC: 11 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1077826

Other (OTH) AF: 0.00 AC: 0 AN: 57836

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000118 AC: 1

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2 Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

autosomal recessive isolated fingernail dysplasia Pathogenic:1

-

University of Washington Center for Mendelian Genomics, University of Washington

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Inherited isolated nail anomaly Pathogenic:1

May 15, 2017

University of Washington Center for Mendelian Genomics, University of Washington

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

not provided Uncertain:1

Jun 12, 2018

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.89	D
Sift4G	Uncertain	0.052	T
Polyphen		0.83	P
Vest4		0.39
MutPred		0.44		Loss of solvent accessibility (P = 0.001);
MVP		0.32
MPC		0.28
ClinPred		0.87	D
GERP RS		3.5
PromoterAI		-0.0073	Neutral
Varity_R		0.23
gMVP		0.35
Mutation Taster		=81/19	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs771745123; hg19: chr10-70287041;