19-3543480-GCCCCCC-GCCCCCCC

Variant names:

• chr19-3543480-G-GC
• rs34196068
• NM_001135580.2:c.322+18dupC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000329493.6(TEKTIP1):​c.322+7_322+8insC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (1049 hom., cov: 0)
  • Exomes 𝑓: 0.13 (632 hom.)
• Consequence: TEKTIP1 ENST00000329493.6 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 19-3543480-G-GC is Benign according to our data. Variant chr19-3543480-G-GC is described in ClinVar as [Benign]. Clinvar id is 403083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKTIP1	NM_001135580.2	c.322+18dupC		intron_variant	Intron 2 of 3	ENST00000329493.6	NP_001129052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKTIP1	ENST00000329493.6	c.322+7_322+8insC		splice_region_variant, intron_variant	Intron 2 of 3	2	NM_001135580.2	ENSP00000327950.4

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 11542 AN: 122904 Hom.: 1049 Cov.: 0

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0905

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0539

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0885

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.0875

GnomAD4 exome AF: 0.131 AC: 154320 AN: 1180436 Hom.: 632 Cov.: 0 AF XY: 0.132 AC XY: 76632 AN XY: 582056

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.0642

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.0907

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.0939 AC: 11545 AN: 122922 Hom.: 1049 Cov.: 0 AF XY: 0.0930 AC XY: 5493 AN XY: 59056

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.0844

Gnomad4 OTH AF: 0.0877

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs34196068; hg19: chr19-3543478;