3-122795430-C-G

Variant names:

• chr3-122795430-C-G
• rs769484443
• NM_032839.3:c.238C>G

Variant summary

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

The NM_032839.3(SLC49A4):​c.238C>G​(p.Arg80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R80C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC49A4 NM_032839.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38774133).

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.238C>G	p.Arg80Gly	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.238C>G	p.Arg80Gly	missense	Exon 1 of 9	ENSP00000261038.5	Q96SL1-1
	SLC49A4	ENST00000477647.1	TSL:1	n.238C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000418554.1	Q05BS2
	SLC49A4	ENST00000864462.1		c.238C>G	p.Arg80Gly	missense	Exon 1 of 10	ENSP00000534521.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455668 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724318

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33308

American (AMR) AF: 0.00 AC: 0 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 85850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4934

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110968

Other (OTH) AF: 0.00 AC: 0 AN: 60180

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	-0.15	T
PhyloP100		2.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.43
Sift	Benign	0.16	T
Sift4G	Benign	0.074	T
Vest4		0.44
MutPred		0.60		Loss of stability (P = 0.0512)
MVP		0.53
MPC		0.39
ClinPred		0.61	D
GERP RS		4.3
PromoterAI		0.066	Neutral
gMVP		0.65
Mutation Taster		=80/20	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: rs769484443; hg19: chr3-122514277;