19-3543480-GCCCCCC-GCCCC

Position:

• chr19-3543480-GCCCCCC-GCCCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135580.2(TEKTIP1):​c.322+17_322+18del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,336,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: TEKTIP1 NM_001135580.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKTIP1	NM_001135580.2	c.322+17_322+18del		splice_region_variant, intron_variant		ENST00000329493.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEKTIP1	ENST00000329493.6	c.322+17_322+18del		splice_region_variant, intron_variant		2	NM_001135580.2	P1
MFSD12	ENST00000398558.8	c.331-505_331-504del		intron_variant		2
MFSD12	ENST00000615073.4	c.490+1327_490+1328del		intron_variant		3
TEKTIP1	ENST00000681976.1	c.163+17_163+18del		splice_region_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 18 AN: 123118 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000469

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000273

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 122 AN: 1213348 Hom.: 0 AF XY: 0.000127 AC XY: 76 AN XY: 598354

Gnomad4 AFR exome AF: 0.000534

Gnomad4 AMR exome AF: 0.0000606

Gnomad4 ASJ exome AF: 0.000181

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.000106

Gnomad4 NFE exome AF: 0.0000837

Gnomad4 OTH exome AF: 0.0000775

GnomAD4 genome AF: 0.000146 AC: 18 AN: 123118 Hom.: 0 Cov.: 0 AF XY: 0.000169 AC XY: 10 AN XY: 59118

Gnomad4 AFR AF: 0.000469

Gnomad4 AMR AF: 0.000159

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000273

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000169

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs34196068; hg19: chr19-3543478;