19-3543480-GCCCCCC-GCCCCCCCCCCCCCCCC

Variant names:

• chr19-3543480-G-GCCCCCCCCCC
• rs34196068
• NM_001135580.2:c.322+9_322+18dupCCCCCCCCCC

Variant summary

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

The ENST00000329493.6(TEKTIP1):​c.322+7_322+8insCCCCCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000032 (0 hom., cov: 0)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TEKTIP1 ENST00000329493.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 0 publications found

Genes affected

TEKTIP1 (HGNC:34496): (tektin bundle interacting protein 1)

MFSD12 (HGNC:28299): (major facilitator superfamily domain containing 12) Enables cysteine transmembrane transporter activity. Involved in cysteine transmembrane transport; pigment metabolic process involved in pigmentation; and regulation of melanin biosynthetic process. Located in lysosome and melanosome. Part of late endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000329493.6. 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
	TEKTIP1	NM_001135580.2	MANE Select	c.322+9_322+18dupCCCCCCCCCC		intron	N/A	NP_001129052.1	A6NCJ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKTIP1	ENST00000329493.6	TSL:2 MANE Select	c.322+7_322+8insCCCCCCCCCC		splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
	MFSD12	ENST00000398558.8	TSL:2	c.329-504_329-503insGGGGGGGGGG		intron	N/A	ENSP00000381566.4	A0A0A0MS91
	MFSD12	ENST00000615073.4	TSL:3	c.490+1328_490+1329insGGGGGGGGGG		intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes AF: 0.0000325 AC: 4 AN: 123130 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000100

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: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.23e-7 AC: 1 AN: 1215596 Hom.: 0 Cov.: 0 AF XY: 0.00000167 AC XY: 1 AN XY: 599434

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

African (AFR) AF: 0.00 AC: 0 AN: 28154

American (AMR) AF: 0.00 AC: 0 AN: 33012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22134

East Asian (EAS) AF: 0.00 AC: 0 AN: 33838

South Asian (SAS) AF: 0.00 AC: 0 AN: 71462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3624

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 933780

Other (OTH) AF: 0.00 AC: 0 AN: 51658

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000325 AC: 4 AN: 123130 Hom.: 0 Cov.: 0 AF XY: 0.0000338 AC XY: 2 AN XY: 59126

African (AFR) AF: 0.000100 AC: 3 AN: 29872

American (AMR) AF: 0.00 AC: 0 AN: 12554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3092

East Asian (EAS) AF: 0.00 AC: 0 AN: 4662

South Asian (SAS) AF: 0.00 AC: 0 AN: 3662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.0000169 AC: 1 AN: 59092

Other (OTH) AF: 0.00 AC: 0 AN: 1652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs34196068; hg19: chr19-3543478;