4-2931067-C-T

Variant names:

• chr4-2931067-C-T
• rs746129513
• NM_001146069.2:c.1246G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001146069.2(SLC75A1):​c.1246G>A​(p.Ala416Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,604,514 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: SLC75A1 NM_001146069.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34169766).

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.1246G>A	p.Ala416Thr	missense	Exon 12 of 13	NP_001139541.1	Q14728
	SLC75A1	NM_001410703.1		c.1246G>A	p.Ala416Thr	missense	Exon 12 of 12	NP_001397632.1	D6RE79
	SLC75A1	NM_001120.5		c.1246G>A	p.Ala416Thr	missense	Exon 11 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.1246G>A	p.Ala416Thr	missense	Exon 12 of 13	ENSP00000347619.4	Q14728
	MFSD10	ENST00000329687.8	TSL:1	c.1246G>A	p.Ala416Thr	missense	Exon 11 of 12	ENSP00000332646.4	Q14728
	MFSD10	ENST00000866678.1		c.1390G>A	p.Ala464Thr	missense	Exon 12 of 13	ENSP00000536737.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000266 AC: 6 AN: 225258 AF XY: 0.0000162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000615

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 29 AN: 1452292 Hom.: 0 Cov.: 31 AF XY: 0.0000208 AC XY: 15 AN XY: 722024

African (AFR) AF: 0.0000301 AC: 1 AN: 33262

American (AMR) AF: 0.0000461 AC: 2 AN: 43374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.0000703 AC: 6 AN: 85312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1108098

Other (OTH) AF: 0.00 AC: 0 AN: 59942

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000451 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000333 AC: 4

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	0.21
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.36
Sift	Benign	0.055	T
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.46		Gain of helix (P = 0.0034)
MVP		0.59
MPC		0.018
ClinPred		0.46	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.41
Mutation Taster		=61/39	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

dbSNP: rs746129513; hg19: chr4-2932794;