4-2931840-C-T

Variant names:

• chr4-2931840-C-T
• rs144214397
• NM_001146069.2:c.899G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001146069.2(SLC75A1):​c.899G>A​(p.Arg300His) variant causes a missense change. The variant allele was found at a frequency of 0.000357 in 1,604,430 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: SLC75A1 NM_001146069.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09799528).

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.899G>A	p.Arg300His	missense	Exon 8 of 13	NP_001139541.1	Q14728
	SLC75A1	NM_001410703.1		c.899G>A	p.Arg300His	missense	Exon 8 of 12	NP_001397632.1	D6RE79
	SLC75A1	NM_001120.5		c.899G>A	p.Arg300His	missense	Exon 7 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.899G>A	p.Arg300His	missense	Exon 8 of 13	ENSP00000347619.4	Q14728
	MFSD10	ENST00000329687.8	TSL:1	c.899G>A	p.Arg300His	missense	Exon 7 of 12	ENSP00000332646.4	Q14728
	MFSD10	ENST00000866678.1		c.1043G>A	p.Arg348His	missense	Exon 8 of 13	ENSP00000536737.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152124 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000383 AC: 89 AN: 232278 AF XY: 0.000398

Gnomad AFR exome AF: 0.000207

Gnomad AMR exome AF: 0.000156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.000348

GnomAD4 exome AF: 0.000364 AC: 529 AN: 1452188 Hom.: 0 Cov.: 34 AF XY: 0.000380 AC XY: 274 AN XY: 721528

African (AFR) AF: 0.000209 AC: 7 AN: 33420

American (AMR) AF: 0.000211 AC: 9 AN: 42660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25854

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39394

South Asian (SAS) AF: 0.000378 AC: 32 AN: 84612

European-Finnish (FIN) AF: 0.000171 AC: 9 AN: 52528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000408 AC: 452 AN: 1107846

Other (OTH) AF: 0.000316 AC: 19 AN: 60116

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22 AN XY: 74424

African (AFR) AF: 0.000169 AC: 7 AN: 41534

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000401 Hom.: 1

Bravo AF: 0.000272

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000437 AC: 53

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.30
Sift	Benign	0.046	D
Sift4G	Uncertain	0.058	T
Polyphen		0.89	P
Vest4		0.40
MVP		0.64
MPC		0.029
ClinPred		0.078	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.64
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144214397; hg19: chr4-2933567;