Genetic Variant NM_025257.3:c.2011+69_2011+72delTTTT (chr6-31864579-CAAAA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_025257.3(SLC44A4):c.2011+69_2011+72delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,130,138 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC44A4
NM_025257.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.323

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal dominant 72
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SLC44A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025257.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC44A4	NM_025257.3	MANE Select	c.2011+69_2011+72delTTTT	intron	N/A	NP_079533.2	A0A140VJH4
SLC44A4	NM_001178044.2		c.1885+69_1885+72delTTTT	intron	N/A	NP_001171515.1	Q53GD3-4
SLC44A4	NM_001178045.2		c.1783+69_1783+72delTTTT	intron	N/A	NP_001171516.1	A0A1U9X8K7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.2011+69_2011+72delTTTT	intron	N/A	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000882851.1		c.2011+69_2011+72delTTTT	intron	N/A	ENSP00000552910.1
SLC44A4	ENST00000882853.1		c.2011+69_2011+72delTTTT	intron	N/A	ENSP00000552912.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

129536

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1130138

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

572844

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000393

AC:

AN:

25432

American (AMR)

AF:

0.00

AC:

AN:

36562

Ashkenazi Jewish (ASJ)

AF:

0.0000441

AC:

AN:

22690

East Asian (EAS)

AF:

0.00

AC:

AN:

37590

South Asian (SAS)

AF:

0.00

AC:

AN:

74804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4248

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

833112

Other (OTH)

AF:

0.00

AC:

AN:

48844

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.235

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

129536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62290

African (AFR)

AF:

0.00

AC:

AN:

36706

American (AMR)

AF:

0.00

AC:

AN:

12848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3070

East Asian (EAS)

AF:

0.00

AC:

AN:

4510

South Asian (SAS)

AF:

0.00

AC:

AN:

4142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

58494

Other (OTH)

AF:

0.00

AC:

AN:

1738

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over