chr19-3543480-GCCCC-G

Variant names:

• chr19-3543480-GCCCC-G
• rs34196068
• NM_001135580.2:c.322+15_322+18delCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000329493.6(TEKTIP1):​c.322+8_322+11delCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000823 in 1,215,534 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: not found (cov: 0)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• 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 2 ACMG points.

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

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+15_322+18delCCCC		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+11delCCCC		splice_region intron	N/A	ENSP00000327950.4	A6NCJ1
	MFSD12	ENST00000398558.8	TSL:2	c.329-507_329-504delGGGG		intron	N/A	ENSP00000381566.4	A0A0A0MS91
	MFSD12	ENST00000615073.4	TSL:3	c.490+1325_490+1328delGGGG		intron	N/A	ENSP00000478456.1	A0A087WU85

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.23e-7 AC: 1 AN: 1215534 Hom.: 0 AF XY: 0.00000167 AC XY: 1 AN XY: 599400

⚠️ 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: 28152

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: 0.00 AC: 0 AN: 933728

Other (OTH) AF: 0.0000194 AC: 1 AN: 51650

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48

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

Other links and lift over

dbSNP: rs34196068; hg19: chr19-3543478;