rs1040813822

Variant names:

• chr3-122795328-C-G
• rs1040813822
• NM_032839.3:c.136C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-122795328-C-G
• chr3-122795328-C-T

Variant summary

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

The NM_032839.3(SLC49A4):​c.136C>G​(p.Arg46Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,365,762 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SLC49A4 NM_032839.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• Publications: 0 publications found

Genes affected

SLC49A4 (HGNC:16628): (solute carrier family 49 member 4) This gene encodes a membrane-bound protein from the major facilitator superfamily of transporters. Disruption of this gene by translocation has been associated with haplo-insufficiency and renal cell carcinomas. Alternatively spliced transcript variants have been described, but their biological validity has not yet been determined. [provided by RefSeq, Jul 2008]

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_032839.3. 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
	SLC49A4	NM_032839.3	MANE Select	c.136C>G	p.Arg46Gly	missense	Exon 1 of 9	NP_116228.1	Q96SL1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC49A4	ENST00000261038.6	TSL:1 MANE Select	c.136C>G	p.Arg46Gly	missense	Exon 1 of 9	ENSP00000261038.5	Q96SL1-1
	SLC49A4	ENST00000477647.1	TSL:1	n.136C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000418554.1	Q05BS2
	SLC49A4	ENST00000864462.1		c.136C>G	p.Arg46Gly	missense	Exon 1 of 10	ENSP00000534521.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1365762 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 677196

African (AFR) AF: 0.00 AC: 0 AN: 27356

American (AMR) AF: 0.00 AC: 0 AN: 27738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23446

East Asian (EAS) AF: 0.0000310 AC: 1 AN: 32218

South Asian (SAS) AF: 0.00 AC: 0 AN: 76580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3946

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076796

Other (OTH) AF: 0.00 AC: 0 AN: 56538

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.51	T
PhyloP100		3.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Vest4		0.42
MutPred		0.64		Gain of sheet (P = 0.0061)
MVP		0.18
MPC		3.1
ClinPred		0.99	D
GERP RS		2.2
PromoterAI		-0.098	Neutral
gMVP		0.80
Mutation Taster		=94/6	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: rs1040813822; hg19: chr3-122514175;