19-3543480-GCCCCCC-GCCCCCCCC

Position:

• chr19-3543480-GCCCCCC-GCCCCCCCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001135580.2(TEKTIP1):​c.322+17_322+18dup 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 0.096 (1407 hom., cov: 0)
  • Exomes 𝑓: 0.083 (541 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEKTIP1	NM_001135580.2	c.322+17_322+18dup		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+18dup		splice_region_variant, intron_variant		2	NM_001135580.2	P1
MFSD12	ENST00000398558.8	c.331-504_331-503insGG		intron_variant		2
MFSD12	ENST00000615073.4	c.490+1328_490+1329insGG		intron_variant		3
TEKTIP1	ENST00000681976.1	c.163+17_163+18dup		splice_region_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.0960 AC: 11774 AN: 122704 Hom.: 1404 Cov.: 0

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0822

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00472

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.0864

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0827 AC: 99211 AN: 1199538 Hom.: 541 Cov.: 0 AF XY: 0.0831 AC XY: 49136 AN XY: 591164

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0875

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.00826

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0568

Gnomad4 NFE exome AF: 0.0811

Gnomad4 OTH exome AF: 0.0891

GnomAD4 genome AF: 0.0960 AC: 11776 AN: 122722 Hom.: 1407 Cov.: 0 AF XY: 0.0923 AC XY: 5442 AN XY: 58968

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0820

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.00474

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0435

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;