10-59654046-A-G

Variant names:

• chr10-59654046-A-G
• NM_194298.3:c.980T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_194298.3(SLC16A9):​c.980T>C​(p.Met327Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SLC16A9 NM_194298.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• Publications: 0 publications found

Genes affected

SLC16A9 (HGNC:23520): (solute carrier family 16 member 9) Predicted to enable monocarboxylic acid transmembrane transporter activity. Involved in urate metabolic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194298.3. 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
	SLC16A9	NM_194298.3	MANE Select	c.980T>C	p.Met327Thr	missense	Exon 5 of 6	NP_919274.1	Q7RTY1
	SLC16A9	NM_001323981.2		c.980T>C	p.Met327Thr	missense	Exon 6 of 7	NP_001310910.1	Q7RTY1
	SLC16A9	NM_001323977.1		c.719T>C	p.Met240Thr	missense	Exon 5 of 6	NP_001310906.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A9	ENST00000395348.8	TSL:5 MANE Select	c.980T>C	p.Met327Thr	missense	Exon 5 of 6	ENSP00000378757.3	Q7RTY1
	SLC16A9	ENST00000881710.1		c.980T>C	p.Met327Thr	missense	Exon 5 of 6	ENSP00000551769.1
	SLC16A9	ENST00000881715.1		c.980T>C	p.Met327Thr	missense	Exon 6 of 7	ENSP00000551774.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461746 Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7 AN XY: 727166

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.021
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.76	N
PhyloP100		8.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.14	T
Polyphen		0.064	B
Vest4		0.84
MutPred		0.53		Gain of phosphorylation at M327 (P = 0.0542)
MVP		0.94
MPC		0.17
ClinPred		0.93	D
GERP RS		4.7
Varity_R		0.60
gMVP		0.80
Mutation Taster		=58/42	polymorphism

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

hg19: chr10-61413804;