NM_052961.4:c.2425G>A

Variant names:

• chr6-35951210-C-T
• rs114153657
• NM_052961.4:c.2425G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_052961.4(SLC26A8):​c.2425G>A​(p.Asp809Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000787 in 1,612,634 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00042 (7 hom.)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.61
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007173419).
• BP6: Variant 6-35951210-C-T is Benign according to our data. Variant chr6-35951210-C-T is described in ClinVar as Benign. ClinVar VariationId is 791537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AD,AR gene

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.2425G>A	p.Asp809Asn	missense	Exon 19 of 20	NP_443193.1	Q96RN1-1
	SLC26A8	NM_001193476.2		c.2425G>A	p.Asp809Asn	missense	Exon 19 of 20	NP_001180405.1	Q96RN1-1
	SLC26A8	NM_138718.3		c.2110G>A	p.Asp704Asn	missense	Exon 17 of 18	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.2425G>A	p.Asp809Asn	missense	Exon 19 of 20	ENSP00000417638.1	Q96RN1-1
	SLC26A8	ENST00000394602.6	TSL:1	c.2110G>A	p.Asp704Asn	missense	Exon 17 of 18	ENSP00000378100.2	Q96RN1-2
	SLC26A8	ENST00000355574.6	TSL:2	c.2425G>A	p.Asp809Asn	missense	Exon 19 of 20	ENSP00000347778.2	Q96RN1-1

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 641 AN: 151452 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00304

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00480

GnomAD2 exomes AF: 0.00108 AC: 272 AN: 251466 AF XY: 0.000758

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000424 AC: 619 AN: 1461060 Hom.: 7 Cov.: 35 AF XY: 0.000347 AC XY: 252 AN XY: 726814

African (AFR) AF: 0.0140 AC: 468 AN: 33456

American (AMR) AF: 0.00116 AC: 52 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86252

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53324

Middle Eastern (MID) AF: 0.000870 AC: 5 AN: 5748

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111500

Other (OTH) AF: 0.000928 AC: 56 AN: 60328

GnomAD4 genome AF: 0.00429 AC: 650 AN: 151574 Hom.: 4 Cov.: 31 AF XY: 0.00411 AC XY: 304 AN XY: 74040

African (AFR) AF: 0.0142 AC: 587 AN: 41312

American (AMR) AF: 0.00304 AC: 46 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10496

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67932

Other (OTH) AF: 0.00475 AC: 10 AN: 2104

Alfa AF: 0.00134 Hom.: 6

Bravo AF: 0.00487

ESP6500AA AF: 0.0132 AC: 58

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00132 AC: 160

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0072	T
MetaSVM	Uncertain	0.73	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.26
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.36
MVP		0.82
MPC		0.78
ClinPred		0.084	T
GERP RS		5.4
Varity_R		0.099
gMVP		0.44
Mutation Taster		=99/1	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: rs114153657; hg19: chr6-35918987; COSMIC: COSV62887765;