3-122806925-A-G

Variant names:

• chr3-122806925-A-G
• rs370093022
• NM_032839.3:c.412A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032839.3(SLC49A4):​c.412A>G​(p.Ile138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,601,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC49A4 NM_032839.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02346459).
• BP6: Variant 3-122806925-A-G is Benign according to our data. Variant chr3-122806925-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3319914.Status of the report is criteria_provided_single_submitter, 1 stars.

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.412A>G	p.Ile138Val	missense	Exon 2 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.412A>G	p.Ile138Val	missense	Exon 2 of 9	ENSP00000261038.5	Q96SL1-1
	SLC49A4	ENST00000477647.1	TSL:1	n.343+11390A>G		intron	N/A	ENSP00000418554.1	Q05BS2
	SLC49A4	ENST00000864462.1		c.412A>G	p.Ile138Val	missense	Exon 2 of 10	ENSP00000534521.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249832 AF XY: 0.00000741

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1449732 Hom.: 0 Cov.: 27 AF XY: 0.00000277 AC XY: 2 AN XY: 721832

African (AFR) AF: 0.0000302 AC: 1 AN: 33162

American (AMR) AF: 0.00 AC: 0 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 85684

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1101906

Other (OTH) AF: 0.0000167 AC: 1 AN: 59954

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152052 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74268

African (AFR) AF: 0.0000966 AC: 4 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.057
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0060
DANN	Benign	0.38
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.043
MVP		0.048
MPC		0.25
ClinPred		0.030	T
GERP RS		-7.7
gMVP		0.36
Mutation Taster		=98/2	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: rs370093022; hg19: chr3-122525772;