4-2930939-C-G

Variant names:

• chr4-2930939-C-G
• rs766585083
• NM_001146069.2:c.1267G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001146069.2(SLC75A1):​c.1267G>C​(p.Gly423Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC75A1 NM_001146069.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

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.1267G>C	p.Gly423Arg	missense	Exon 13 of 13	NP_001139541.1	Q14728
	SLC75A1	NM_001120.5		c.1267G>C	p.Gly423Arg	missense	Exon 12 of 12	NP_001111.3
	SLC75A1	NM_001410703.1		c.1374G>C	p.Pro458Pro	synonymous	Exon 12 of 12	NP_001397632.1	D6RE79

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD10	ENST00000355443.9	TSL:1 MANE Select	c.1267G>C	p.Gly423Arg	missense	Exon 13 of 13	ENSP00000347619.4	Q14728
	MFSD10	ENST00000329687.8	TSL:1	c.1267G>C	p.Gly423Arg	missense	Exon 12 of 12	ENSP00000332646.4	Q14728
	MFSD10	ENST00000866678.1		c.1411G>C	p.Gly471Arg	missense	Exon 13 of 13	ENSP00000536737.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Pathogenic	0.75
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.83		Gain of MoRF binding (P = 0.0478)
MVP		0.66
MPC		0.16
ClinPred		1.0	D
GERP RS		3.1
Varity_R		0.75
gMVP		0.61
Mutation Taster		=67/33	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: rs766585083; hg19: chr4-2932666;