22-38078443-TCGCCCCGGGCG-T

Variant names:

• chr22-38078443-TCGCCCCGGGCG-T
• rs140740838
• NM_013356.3:c.1449_1459delCGCCCGGGGCG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_013356.3(SLC16A8):​c.1449_1459delCGCCCGGGGCG​(p.Ser483ArgfsTer30) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000695 in 1,612,058 control chromosomes in the GnomAD database, including 11 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (8 hom.)
• Consequence: SLC16A8 NM_013356.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.36
• Publications: 1 publications found

Genes affected

SLC16A8 (HGNC:16270): (solute carrier family 16 member 8) SLC16A8 is a member of a family of proton-coupled monocarboxylate transporters that mediate lactate transport across cell membranes (Yoon et al., 1999 [PubMed 10493836]).[supplied by OMIM, Apr 2010]

LOC105373027 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 22-38078443-TCGCCCCGGGCG-T is Benign according to our data. Variant chr22-38078443-TCGCCCCGGGCG-T is described in ClinVar as Benign. ClinVar VariationId is 714907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013356.3. 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
	SLC16A8	NM_013356.3	MANE Select	c.1449_1459delCGCCCGGGGCG	p.Ser483ArgfsTer30	frameshift	Exon 6 of 6	NP_037488.2	O95907
	SLC16A8	NM_001394131.1		c.171_181delCGCCCGGGGCG	p.Ser57ArgfsTer30	frameshift	Exon 2 of 2	NP_001381060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A8	ENST00000681075.2	MANE Select	c.1449_1459delCGCCCGGGGCG	p.Ser483ArgfsTer30	frameshift	Exon 6 of 6	ENSP00000506669.1	O95907
	SLC16A8	ENST00000320521.10	TSL:1	c.1449_1459delCGCCCGGGGCG	p.Ser483ArgfsTer30	frameshift	Exon 5 of 5	ENSP00000321735.5	O95907
	SLC16A8	ENST00000902580.1		c.1449_1459delCGCCCGGGGCG	p.Ser483ArgfsTer30	frameshift	Exon 5 of 5	ENSP00000572639.1

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 555 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000967 AC: 241 AN: 249284 AF XY: 0.000763

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000387 AC: 565 AN: 1459730 Hom.: 8 AF XY: 0.000353 AC XY: 256 AN XY: 726224

African (AFR) AF: 0.0150 AC: 502 AN: 33468

American (AMR) AF: 0.000514 AC: 23 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111798

Other (OTH) AF: 0.000563 AC: 34 AN: 60376

GnomAD4 genome AF: 0.00364 AC: 555 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00328 AC XY: 244 AN XY: 74476

African (AFR) AF: 0.0130 AC: 539 AN: 41578

American (AMR) AF: 0.000588 AC: 9 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.00391

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=72/128	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140740838; hg19: chr22-38474450;