NM_033051.4:c.777T>C

Variant names:

• chr9-112889905-A-G
• rs7021942
• NM_033051.4:c.777T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_033051.4(SLC46A2):​c.777T>C​(p.Asp259Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,614,220 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (8 hom.)
• Consequence: SLC46A2 NM_033051.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.169
• Publications: 1 publications found

Genes affected

SLC46A2 (HGNC:16055): (solute carrier family 46 member 2) Predicted to enable transmembrane transporter activity. Involved in positive regulation of nucleotide-binding activity oligomerization domain containing 1 signaling pathway. Predicted to be located in cell surface and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-112889905-A-G is Benign according to our data. Variant chr9-112889905-A-G is described in ClinVar as Benign. ClinVar VariationId is 778963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.169 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00521 (794/152326) while in subpopulation AFR AF = 0.0161 (669/41562). AF 95% confidence interval is 0.0151. There are 7 homozygotes in GnomAd4. There are 365 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033051.4. 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
	SLC46A2	NM_033051.4	MANE Select	c.777T>C	p.Asp259Asp	synonymous	Exon 1 of 4	NP_149040.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC46A2	ENST00000374228.5	TSL:1 MANE Select	c.777T>C	p.Asp259Asp	synonymous	Exon 1 of 4	ENSP00000363345.4	Q9BY10
	SLC46A2	ENST00000868988.1		c.777T>C	p.Asp259Asp	synonymous	Exon 1 of 4	ENSP00000539047.1
	SLC46A2	ENST00000491462.2	TSL:5	n.777T>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000474847.1	S4R3Y2

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 793 AN: 152208 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00224 AC: 564 AN: 251466 AF XY: 0.00164

Gnomad AFR exome AF: 0.0194

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.00565

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000580

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000895 AC: 1308 AN: 1461894 Hom.: 8 Cov.: 31 AF XY: 0.000821 AC XY: 597 AN XY: 727248

African (AFR) AF: 0.0149 AC: 500 AN: 33480

American (AMR) AF: 0.00356 AC: 159 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00551 AC: 144 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.000307 AC: 341 AN: 1112012

Other (OTH) AF: 0.00228 AC: 138 AN: 60396

GnomAD4 genome AF: 0.00521 AC: 794 AN: 152326 Hom.: 7 Cov.: 32 AF XY: 0.00490 AC XY: 365 AN XY: 74482

African (AFR) AF: 0.0161 AC: 669 AN: 41562

American (AMR) AF: 0.00353 AC: 54 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68038

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00281 Hom.: 2

Bravo AF: 0.00616

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.44
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7021942; hg19: chr9-115652185;