NM_052961.4:c.2447G>C

Variant names:

• chr6-35951188-C-G
• rs116200048
• NM_052961.4:c.2447G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052961.4(SLC26A8):​c.2447G>C​(p.Arg816Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R816W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 5 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35011426).

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.2447G>C	p.Arg816Pro	missense	Exon 19 of 20	NP_443193.1	Q96RN1-1
	SLC26A8	NM_001193476.2		c.2447G>C	p.Arg816Pro	missense	Exon 19 of 20	NP_001180405.1	Q96RN1-1
	SLC26A8	NM_138718.3		c.2132G>C	p.Arg711Pro	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.2447G>C	p.Arg816Pro	missense	Exon 19 of 20	ENSP00000417638.1	Q96RN1-1
	SLC26A8	ENST00000394602.6	TSL:1	c.2132G>C	p.Arg711Pro	missense	Exon 17 of 18	ENSP00000378100.2	Q96RN1-2
	SLC26A8	ENST00000355574.6	TSL:2	c.2447G>C	p.Arg816Pro	missense	Exon 19 of 20	ENSP00000347778.2	Q96RN1-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251422 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461788 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.21
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.023	D
Polyphen		0.56	P
Vest4		0.41
MutPred		0.23		Gain of glycosylation at T813 (P = 0.0327)
MVP		0.62
MPC		0.41
ClinPred		0.68	D
GERP RS		1.3
Varity_R		0.49
gMVP		0.68
Mutation Taster		=57/43	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: rs116200048; hg19: chr6-35918965;