chr4-2931429-C-T

Variant names:

• chr4-2931429-C-T
• rs763621840
• NM_001146069.2:c.1060G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001146069.2(SLC75A1):​c.1060G>A​(p.Gly354Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000623 in 1,557,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: SLC75A1 NM_001146069.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70
• Publications: 0 publications found

Genes affected

SLC75A1 (HGNC:16894): (major facilitator superfamily domain containing 10) This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein likely functions in efflux of organic anions, including the non-steroidal anti-inflammatory drugs indomethacin and diclofenac. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

ACMG classification

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

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146069.2. 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
	SLC75A1	NM_001146069.2	MANE Select	c.1060G>A	p.Gly354Ser	missense	Exon 10 of 13	NP_001139541.1	Q14728
	SLC75A1	NM_001410703.1		c.1060G>A	p.Gly354Ser	missense	Exon 10 of 12	NP_001397632.1	D6RE79
	SLC75A1	NM_001120.5		c.1060G>A	p.Gly354Ser	missense	Exon 9 of 12	NP_001111.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD10	ENST00000355443.9	TSL:1 MANE Select	c.1060G>A	p.Gly354Ser	missense	Exon 10 of 13	ENSP00000347619.4	Q14728
	MFSD10	ENST00000329687.8	TSL:1	c.1060G>A	p.Gly354Ser	missense	Exon 9 of 12	ENSP00000332646.4	Q14728
	MFSD10	ENST00000866678.1		c.1204G>A	p.Gly402Ser	missense	Exon 10 of 13	ENSP00000536737.1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000245 AC: 4 AN: 163192 AF XY: 0.0000345

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000396

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000311

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000598 AC: 84 AN: 1405306 Hom.: 0 Cov.: 34 AF XY: 0.0000519 AC XY: 36 AN XY: 694208

African (AFR) AF: 0.0000314 AC: 1 AN: 31808

American (AMR) AF: 0.0000276 AC: 1 AN: 36170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25210

East Asian (EAS) AF: 0.000139 AC: 5 AN: 36050

South Asian (SAS) AF: 0.0000249 AC: 2 AN: 80314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48522

Middle Eastern (MID) AF: 0.00316 AC: 18 AN: 5692

European-Non Finnish (NFE) AF: 0.0000508 AC: 55 AN: 1083210

Other (OTH) AF: 0.0000343 AC: 2 AN: 58330

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152086 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74280

African (AFR) AF: 0.0000483 AC: 2 AN: 41414

American (AMR) AF: 0.000262 AC: 4 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000390 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000174 AC: 2

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	Benign	0.19
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.39	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	2.0	M
PhyloP100		5.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.4	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.81
MVP		0.63
MPC		0.15
ClinPred		0.88	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.69
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs763621840; hg19: chr4-2933156;