rs112262188

Variant names:

• chr17-68271344-G-C
• rs112262188
• NM_004694.5:c.816C>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004694.5(SLC16A6):​c.816C>G​(p.Thr272Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,614,250 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: SLC16A6 NM_004694.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00700
• Publications: 1 publications found

Genes affected

SLC16A6 (HGNC:10927): (solute carrier family 16 member 6) Predicted to enable monocarboxylic acid transmembrane transporter activity. Predicted to be involved in monocarboxylic acid transport. Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARSG (HGNC:24102): (arylsulfatase G) The protein encoded by this gene belongs to the sulfatase enzyme family. Sulfatases hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules. This protein displays arylsulfatase activity at acidic pH, as is typical of lysosomal sulfatases, and has been shown to localize in the lysosomes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

ARSG Gene-Disease associations (from GenCC):

• Usher syndrome, type 4

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Usher syndrome type 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-68271344-G-C is Benign according to our data. Variant chr17-68271344-G-C is described in ClinVar as Benign. ClinVar VariationId is 717112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.007 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004694.5. 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
	SLC16A6	NM_004694.5	MANE Select	c.816C>G	p.Thr272Thr	synonymous	Exon 5 of 6	NP_004685.2
	SLC16A6	NM_001174166.2		c.816C>G	p.Thr272Thr	synonymous	Exon 6 of 7	NP_001167637.1	O15403
	ARSG	NM_014960.5		c.-552+11918G>C		intron	N/A	NP_055775.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A6	ENST00000580666.6	TSL:1 MANE Select	c.816C>G	p.Thr272Thr	synonymous	Exon 5 of 6	ENSP00000462985.1	O15403
	SLC16A6	ENST00000327268.8	TSL:1	c.816C>G	p.Thr272Thr	synonymous	Exon 6 of 7	ENSP00000319991.4	O15403
	ARSG	ENST00000448504.6	TSL:1	c.-552+11918G>C		intron	N/A	ENSP00000407193.2	Q96EG1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 237 AN: 152244 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00896

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00148 AC: 372 AN: 251430 AF XY: 0.00139

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00564

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00120

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00102 AC: 1487 AN: 1461888 Hom.: 3 Cov.: 31 AF XY: 0.000993 AC XY: 722 AN XY: 727244

African (AFR) AF: 0.00143 AC: 48 AN: 33480

American (AMR) AF: 0.00608 AC: 272 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26136

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

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.00745 AC: 43 AN: 5768

European-Non Finnish (NFE) AF: 0.000857 AC: 953 AN: 1112008

Other (OTH) AF: 0.00243 AC: 147 AN: 60396

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152362 Hom.: 4 Cov.: 32 AF XY: 0.00170 AC XY: 127 AN XY: 74508

African (AFR) AF: 0.000697 AC: 29 AN: 41584

American (AMR) AF: 0.00895 AC: 137 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68032

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

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.00225

EpiCase AF: 0.00136

EpiControl AF: 0.00190

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	-0.86
CADD	Benign	0.19
DANN	Benign	0.54
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs112262188; hg19: chr17-66267485;