6-35835334-CTC-TTT

Variant names:

• chr6-35835334-CTC-TTT
• NM_003137.5:c.1936_1938delGAGinsAAA
• SRPK1 p.Glu646Lys

Variant summary

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

The NM_003137.5(SRPK1):​c.1936_1938delGAGinsAAA​(p.Glu646Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRPK1 NM_003137.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.21
• Publications: 0 publications found

Genes affected

SRPK1 (HGNC:11305): (SRSF protein kinase 1) This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined.[provided by RefSeq, Jul 2010]

LHFPL5 (HGNC:21253): (LHFPL tetraspan subfamily member 5) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in this gene result in deafness in humans, and a mutation in a similar gene in mice results in deafness and vestibular dysfunction with severe degeneration of the organ of Corti. It is proposed to function in hair bundle morphogenesis. [provided by RefSeq, Jul 2008]

LHFPL5 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 67

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003137.5. 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
	SRPK1	NM_003137.5	MANE Select	c.1936_1938delGAGinsAAA	p.Glu646Lys	missense	N/A	NP_003128.3
	SRPK1	NR_034069.2		n.2006_2008delGAGinsAAA		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPK1	ENST00000373825.7	TSL:1 MANE Select	c.1936_1938delGAGinsAAA	p.Glu646Lys	missense	N/A	ENSP00000362931.2	Q96SB4-2
	SRPK1	ENST00000361690.7	TSL:1	c.1984_1986delGAGinsAAA	p.Glu662Lys	missense	N/A	ENSP00000354674.3	H3BLV9
	SRPK1	ENST00000423325.6	TSL:2	c.1888_1890delGAGinsAAA	p.Glu630Lys	missense	N/A	ENSP00000391069.2	Q96SB4-4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-35803111;