chr11-65538885-G-A

Variant names:

• chr11-65538885-G-A
• rs11545201
• NM_001130144.3:c.*195C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001130144.3(LTBP3):​c.*195C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,074,382 control chromosomes in the GnomAD database, including 1,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (799 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (376 hom.)
• Consequence: LTBP3 NM_001130144.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.17
• Publications: 3 publications found

Genes affected

LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

SCYL1 (HGNC:14372): (SCY1 like pseudokinase 1) This gene encodes a transcriptional regulator belonging to the SCY1-like family of kinase-like proteins. The protein has a divergent N-terminal kinase domain that is thought to be catalytically inactive, and can bind specific DNA sequences through its C-terminal domain. It activates transcription of the telomerase reverse transcriptase and DNA polymerase beta genes. The protein has been localized to the nucleus, and also to the cytoplasm and centrosomes during mitosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SCYL1 Gene-Disease associations (from GenCC):

• acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-65538885-G-A is Benign according to our data. Variant chr11-65538885-G-A is described in ClinVar as Benign. ClinVar VariationId is 1241986.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130144.3. 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
	LTBP3	NM_001130144.3	MANE Select	c.*195C>T		3_prime_UTR	Exon 28 of 28	NP_001123616.1	Q9NS15-1
	LTBP3	NM_021070.4		c.*195C>T		3_prime_UTR	Exon 27 of 27	NP_066548.2	Q9NS15-2
	LTBP3	NM_001164266.1		c.*195C>T		3_prime_UTR	Exon 27 of 27	NP_001157738.1	Q9NS15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP3	ENST00000301873.11	TSL:2 MANE Select	c.*195C>T		3_prime_UTR	Exon 28 of 28	ENSP00000301873.5	Q9NS15-1
	LTBP3	ENST00000322147.8	TSL:1	c.*195C>T		3_prime_UTR	Exon 27 of 27	ENSP00000326647.4	Q9NS15-2
	LTBP3	ENST00000971648.1		c.*195C>T		3_prime_UTR	Exon 28 of 28	ENSP00000641707.1

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8333 AN: 152140 Hom.: 799 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00473 AC: 4364 AN: 922124 Hom.: 376 Cov.: 12 AF XY: 0.00419 AC XY: 1885 AN XY: 449958

African (AFR) AF: 0.189 AC: 3454 AN: 18318

American (AMR) AF: 0.0126 AC: 142 AN: 11292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14554

East Asian (EAS) AF: 0.00 AC: 0 AN: 26876

South Asian (SAS) AF: 0.000366 AC: 15 AN: 40976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26686

Middle Eastern (MID) AF: 0.00688 AC: 19 AN: 2762

European-Non Finnish (NFE) AF: 0.000336 AC: 249 AN: 741186

Other (OTH) AF: 0.0123 AC: 485 AN: 39474

GnomAD4 genome AF: 0.0548 AC: 8343 AN: 152258 Hom.: 799 Cov.: 33 AF XY: 0.0522 AC XY: 3884 AN XY: 74466

African (AFR) AF: 0.191 AC: 7945 AN: 41532

American (AMR) AF: 0.0191 AC: 293 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68008

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.0366 Hom.: 192

Bravo AF: 0.0625

Asia WGS AF: 0.00953 AC: 34 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.086
DANN	Benign	0.87
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11545201; hg19: chr11-65306356;