Genetic Variant NM_000112.4:c.25C>T (chr5-149977677-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000112.4(SLC26A2):c.25C>T(p.His9Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

SLC26A2
NM_000112.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.847

Variant links:

Genes affected

SLC26A2 (HGNC:10994): (solute carrier family 26 member 2) The diastrophic dysplasia sulfate transporter is a transmembrane glycoprotein implicated in the pathogenesis of several human chondrodysplasias. It apparently is critical in cartilage for sulfation of proteoglycans and matrix organization. [provided by RefSeq, Jul 2008]

SLC26A2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061398983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A2	NM_000112.4 link	c.25C>T	p.His9Tyr	missense_variant	Exon 2 of 3	ENST00000286298.5	NP_000103.2	P50443
SLC26A2	XM_017009191.3 link	c.25C>T	p.His9Tyr	missense_variant	Exon 2 of 4		XP_016864680.1	P50443

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A2	ENST00000286298.5 link	c.25C>T	p.His9Tyr	missense_variant	Exon 2 of 3	1	NM_000112.4	ENSP00000286298.4	P50443
SLC26A2	ENST00000433184.1 link	c.25C>T	p.His9Tyr	missense_variant	Exon 3 of 3	4		ENSP00000405496.1	C9JAN6
SLC26A2	ENST00000690410.1 link	n.257C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250686

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.40

T;.

M_CAP

Benign

0.074

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.28

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.71

N;D

REVEL

Benign

0.22

Sift

Benign

0.12

T;.

Sift4G

Uncertain

0.022

D;.

Polyphen

0.17

B;.

Vest4

0.12

MVP

0.65

MPC

0.052

ClinPred

0.11

GERP RS

1.9

Varity_R

0.064

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over