chr6-35944492-A-G

Variant names:

• chr6-35944492-A-G
• rs7746080
• NM_052961.4:c.2473-152T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052961.4(SLC26A8):​c.2473-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 415,620 control chromosomes in the GnomAD database, including 5,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (4062 hom., cov: 31)
  • Exomes 𝑓: 0.073 (1385 hom.)
• Consequence: SLC26A8 NM_052961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150
• Publications: 0 publications found

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

SLC26A8 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
• spermatogenic failure 3

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000304790 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 6-35944492-A-G is Benign according to our data. Variant chr6-35944492-A-G is described in ClinVar as Benign. ClinVar VariationId is 1280228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052961.4. 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
	SLC26A8	NM_052961.4	MANE Select	c.2473-152T>C		intron	N/A	NP_443193.1	Q96RN1-1
	SLC26A8	NM_001193476.2		c.2473-152T>C		intron	N/A	NP_001180405.1	Q96RN1-1
	SLC26A8	NM_138718.3		c.2158-152T>C		intron	N/A	NP_619732.2	Q96RN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A8	ENST00000490799.6	TSL:1 MANE Select	c.2473-152T>C		intron	N/A	ENSP00000417638.1	Q96RN1-1
	SLC26A8	ENST00000394602.6	TSL:1	c.2158-152T>C		intron	N/A	ENSP00000378100.2	Q96RN1-2
	SLC26A8	ENST00000355574.6	TSL:2	c.2473-152T>C		intron	N/A	ENSP00000347778.2	Q96RN1-1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25451 AN: 149840 Hom.: 4040 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0643

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.0730 AC: 19407 AN: 265732 Hom.: 1385 AF XY: 0.0718 AC XY: 9847 AN XY: 137160

African (AFR) AF: 0.410 AC: 3374 AN: 8220

American (AMR) AF: 0.109 AC: 1150 AN: 10508

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 963 AN: 9326

East Asian (EAS) AF: 0.0443 AC: 1033 AN: 23318

South Asian (SAS) AF: 0.0574 AC: 503 AN: 8766

European-Finnish (FIN) AF: 0.0515 AC: 997 AN: 19360

Middle Eastern (MID) AF: 0.129 AC: 162 AN: 1258

European-Non Finnish (NFE) AF: 0.0570 AC: 9590 AN: 168292

Other (OTH) AF: 0.0980 AC: 1635 AN: 16684

GnomAD4 genome AF: 0.170 AC: 25500 AN: 149888 Hom.: 4062 Cov.: 31 AF XY: 0.168 AC XY: 12258 AN XY: 73136

African (AFR) AF: 0.423 AC: 17333 AN: 40976

American (AMR) AF: 0.129 AC: 1930 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3472

East Asian (EAS) AF: 0.0641 AC: 330 AN: 5148

South Asian (SAS) AF: 0.0918 AC: 438 AN: 4772

European-Finnish (FIN) AF: 0.0583 AC: 564 AN: 9670

Middle Eastern (MID) AF: 0.140 AC: 40 AN: 286

European-Non Finnish (NFE) AF: 0.0586 AC: 3963 AN: 67642

Other (OTH) AF: 0.184 AC: 378 AN: 2058

Alfa AF: 0.121 Hom.: 314

Bravo AF: 0.189

Asia WGS AF: 0.0980 AC: 339 AN: 3476

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
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.6
DANN	Benign	0.76
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs7746080; hg19: chr6-35912269;