3-41455578-T-C

Variant names:

• chr3-41455578-T-C
• rs142834126
• NM_017886.4:c.3411A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_017886.4(ULK4):​c.3411A>G​(p.Ser1137Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,613,916 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (4 hom.)
• Consequence: ULK4 NM_017886.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.454

Genes affected

ULK4 (HGNC:15784): (unc-51 like kinase 4) This gene encodes a member of the unc-51-like serine/threonine kinase (STK) family. Members of this protein family play a role in neuronal growth and endocytosis. The encoded protein is likely involved in neurite branching, neurite elongation and neuronal migration. Genome-wide association studies (GWAS) indicate an association of variations in this gene with blood pressure and hypertension. Sequence variations in this gene may also be be associated with psychiatric disorders, including schizophrenia and bipolar disorder. Pseudogenes associated with this gene have been identified and are located on chromosome 15. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 3-41455578-T-C is Benign according to our data. Variant chr3-41455578-T-C is described in ClinVar as [Benign]. Clinvar id is 783999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.454 with no splicing effect.
• BS2: High AC in GnomAd4 at 671 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.3411A>G	p.Ser1137Ser	synonymous_variant	Exon 34 of 37	ENST00000301831.9	NP_060356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.3411A>G	p.Ser1137Ser	synonymous_variant	Exon 34 of 37	2	NM_017886.4	ENSP00000301831.4

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 671 AN: 152172 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

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: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.000964 AC: 240 AN: 248978 AF XY: 0.000785

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000423 AC: 618 AN: 1461626 Hom.: 4 Cov.: 30 AF XY: 0.000374 AC XY: 272 AN XY: 727110

African (AFR) AF: 0.0157 AC: 524 AN: 33464

American (AMR) AF: 0.000626 AC: 28 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111884

Other (OTH) AF: 0.000927 AC: 56 AN: 60386

GnomAD4 genome AF: 0.00441 AC: 671 AN: 152290 Hom.: 4 Cov.: 32 AF XY: 0.00454 AC XY: 338 AN XY: 74452

African (AFR) AF: 0.0155 AC: 644 AN: 41576

American (AMR) AF: 0.000981 AC: 15 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00191 Hom.: 0

Bravo AF: 0.00509

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 10, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.010
DANN	Benign	0.59
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

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Other links and lift over

dbSNP: rs142834126; hg19: chr3-41497069;