Variant chr6-31864811-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_025257.3(SLC44A4):c.1926+5G>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000396 in 1,613,996 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 1 hom. )

Consequence

SLC44A4
NM_025257.3 splice_region, intron

Scores

Splicing: ADA: 0.9995

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.80

Variant links:

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC44A4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 6-31864811-C-A is Benign according to our data. Variant chr6-31864811-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1596993.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLC44A4	NM_025257.3 linkuse as main transcript	c.1926+5G>T	splice_region_variant, intron_variant	ENST00000229729.11	NP_079533.2	Q53GD3-1A0A140VJH4
SLC44A4	NM_001178044.2 linkuse as main transcript	c.1800+5G>T	splice_region_variant, intron_variant		NP_001171515.1	Q53GD3-4
SLC44A4	NM_001178045.2 linkuse as main transcript	c.1698+5G>T	splice_region_variant, intron_variant		NP_001171516.1	Q53GD3-3A0A1U9X8K7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SLC44A4	ENST00000229729.11 linkuse as main transcript	c.1926+5G>T	splice_region_variant, intron_variant	1	NM_025257.3	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000375562.8 linkuse as main transcript	c.1800+5G>T	splice_region_variant, intron_variant	2		ENSP00000364712.4	Q53GD3-4
SLC44A4	ENST00000544672.5 linkuse as main transcript	c.1698+5G>T	splice_region_variant, intron_variant	2		ENSP00000444109.1	Q53GD3-3

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00652

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000752

AC:

189

AN:

251234

Hom.:

AF XY:

0.000729

AC XY:

AN XY:

135838

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00642

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000365

AC:

533

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

278

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00556

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000697

AC:

106

AN:

152142

Hom.:

Cov.:

AF XY:

0.000982

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00652

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000438

Hom.:

Bravo

AF:

0.000230

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.82

SpliceAI score (max)

0.88

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -39

DS_DL_spliceai

0.88

Position offset: 5

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over