19-3543480-GCCCCCC-GC

Variant names:

• chr19-3543480-GCCCCC-G
• rs34196068
• NM_001135580.2:c.322+14_322+18delCCCCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000329493.6(TEKTIP1):​c.322+8_322+12delCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,338,738 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00085 (2 hom., cov: 0)
  • Exomes 𝑓: 0.000077 (1 hom.)
• Consequence: TEKTIP1 ENST00000329493.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 gene

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+14_322+18delCCCCC		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+8_322+12delCCCCC		splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
	MFSD12	ENST00000398558.8	TSL:2	c.329-508_329-504delGGGGG		intron	N/A	ENSP00000381566.4	A0A0A0MS91
	MFSD12	ENST00000615073.4	TSL:3	c.490+1324_490+1328delGGGGG		intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes AF: 0.000845 AC: 104 AN: 123130 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000239

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: 0.0000765 AC: 93 AN: 1215592 Hom.: 1 AF XY: 0.0000667 AC XY: 40 AN XY: 599432

African (AFR) AF: 0.00266 AC: 75 AN: 28154

American (AMR) AF: 0.000303 AC: 10 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: 0.0000280 AC: 2 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: 0.00000214 AC: 2 AN: 933776

Other (OTH) AF: 0.0000774 AC: 4 AN: 51658

GnomAD4 genome AF: 0.000853 AC: 105 AN: 123146 Hom.: 2 Cov.: 0 AF XY: 0.000794 AC XY: 47 AN XY: 59168

African (AFR) AF: 0.00337 AC: 101 AN: 29928

American (AMR) AF: 0.000239 AC: 3 AN: 12568

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4642

South Asian (SAS) AF: 0.00 AC: 0 AN: 3650

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.0000169 AC: 1 AN: 59082

Other (OTH) AF: 0.00 AC: 0 AN: 1660

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism

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;