chr17-74790238-C-T

Variant names:

• chr17-74790238-C-T
• rs117699067
• NM_017728.4:c.288C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_017728.4(SLC38A12):​c.288C>T​(p.Ser96Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,614,040 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (15 hom., cov: 30)
  • Exomes 𝑓: 0.015 (181 hom.)
• Consequence: SLC38A12 NM_017728.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.450
• Publications: 4 publications found

Genes affected

SLC38A12 (HGNC:25984): (transmembrane protein 104) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A12 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 17-74790238-C-T is Benign according to our data. Variant chr17-74790238-C-T is described in ClinVar as Benign. ClinVar VariationId is 773593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.45 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0108 (1638/152298) while in subpopulation NFE AF = 0.0169 (1149/68012). AF 95% confidence interval is 0.0161. There are 15 homozygotes in GnomAd4. There are 777 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1638 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017728.4. 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
	SLC38A12	NM_017728.4	MANE Select	c.288C>T	p.Ser96Ser	synonymous	Exon 5 of 10	NP_060198.3
	SLC38A12	NM_001321264.3		c.288C>T	p.Ser96Ser	synonymous	Exon 5 of 10	NP_001308193.1	Q8NE00-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM104	ENST00000335464.10	TSL:1 MANE Select	c.288C>T	p.Ser96Ser	synonymous	Exon 5 of 10	ENSP00000334849.5	Q8NE00-1
	TMEM104	ENST00000915164.1		c.327C>T	p.Ser109Ser	synonymous	Exon 5 of 10	ENSP00000585223.1
	TMEM104	ENST00000582330.2	TSL:2	c.288C>T	p.Ser96Ser	synonymous	Exon 5 of 10	ENSP00000461922.1	Q8NE00-1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1638 AN: 152180 Hom.: 15 Cov.: 30

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0108 AC: 2706 AN: 251438 AF XY: 0.0108

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.00899

Gnomad ASJ exome AF: 0.00804

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.0150 AC: 21888 AN: 1461742 Hom.: 181 Cov.: 31 AF XY: 0.0145 AC XY: 10561 AN XY: 727190

African (AFR) AF: 0.00239 AC: 80 AN: 33480

American (AMR) AF: 0.00890 AC: 398 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00746 AC: 195 AN: 26134

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39696

South Asian (SAS) AF: 0.00153 AC: 132 AN: 86258

European-Finnish (FIN) AF: 0.00939 AC: 501 AN: 53368

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5766

European-Non Finnish (NFE) AF: 0.0178 AC: 19819 AN: 1111922

Other (OTH) AF: 0.0121 AC: 728 AN: 60394

GnomAD4 genome AF: 0.0108 AC: 1638 AN: 152298 Hom.: 15 Cov.: 30 AF XY: 0.0104 AC XY: 777 AN XY: 74470

African (AFR) AF: 0.00272 AC: 113 AN: 41580

American (AMR) AF: 0.0103 AC: 158 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0169 AC: 1149 AN: 68012

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0135 Hom.: 11

Bravo AF: 0.0101

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0153

EpiControl AF: 0.0139

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	-0.25
CADD	Benign	5.7
DANN	Benign	0.86
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs117699067; hg19: chr17-72786377;