chr4-128969635-T-C

Variant names:

• chr4-128969635-T-C
• rs7655841
• NM_144643.4:c.777+743A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144643.4(SCLT1):​c.777+743A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,010 control chromosomes in the GnomAD database, including 6,836 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6836 hom., cov: 32)
• Consequence: SCLT1 NM_144643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 8 publications found

Genes affected

SCLT1 (HGNC:26406): (sodium channel and clathrin linker 1) This gene encodes an adaptor protein. Studies of a related gene in rat suggest that the encoded protein functions to link clathrin to the sodium channel protein type 10 subunit alpha protein. The encoded protein has also been identified as a component of distal appendages of centrioles that is necessary for ciliogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

SCLT1 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• Bardet-Biedl syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox
• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P
• Senior-Loken syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144643.4. 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
	SCLT1	NM_144643.4	MANE Select	c.777+743A>G		intron	N/A	NP_653244.2	Q96NL6-1
	SCLT1	NM_001410807.1		c.777+743A>G		intron	N/A	NP_001397736.1	A0A494C0G8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCLT1	ENST00000281142.10	TSL:2 MANE Select	c.777+743A>G		intron	N/A	ENSP00000281142.5	Q96NL6-1
	SCLT1	ENST00000503215.5	TSL:1	c.617+22532A>G		intron	N/A	ENSP00000424029.1	D6RBP0
	SCLT1	ENST00000439369.6	TSL:1	c.290+69406A>G		intron	N/A	ENSP00000395292.2	Q96NL6-3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40153 AN: 151892 Hom.: 6840 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.271

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.264 AC: 40187 AN: 152010 Hom.: 6836 Cov.: 32 AF XY: 0.260 AC XY: 19324 AN XY: 74334

African (AFR) AF: 0.480 AC: 19891 AN: 41440

American (AMR) AF: 0.250 AC: 3822 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1357 AN: 5162

South Asian (SAS) AF: 0.105 AC: 507 AN: 4828

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10590

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11676 AN: 67940

Other (OTH) AF: 0.270 AC: 568 AN: 2106

Alfa AF: 0.227 Hom.: 1629

Bravo AF: 0.288

Asia WGS AF: 0.201 AC: 700 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.58
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism (auto)

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: rs7655841; hg19: chr4-129890790;