17-15999624-G-A

Variant names:

• chr17-15999624-G-A
• rs779218631
• NM_001042697.2:c.-30C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042697.2(ZSWIM7):​c.-30C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000354 in 1,413,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ZSWIM7 NM_001042697.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 0 publications found

Genes affected

ZSWIM7 (HGNC:26993): (zinc finger SWIM-type containing 7) Predicted to enable zinc ion binding activity. Involved in double-strand break repair via homologous recombination and protein stabilization. Part of Shu complex. [provided by Alliance of Genome Resources, Apr 2022]

TTC19 (HGNC:26006): (tetratricopeptide repeat domain 19) This gene encodes a protein with a tetratricopeptide repeat (TPR) domain containing several TPRs of about 34 aa each. These repeats are found in a variety of organisms including bacteria, fungi and plants, and are involved in a variety of functions including protein-protein interactions. This protein is embedded in the inner mitochondrial membrane and is involved in the formation of the mitochondrial respiratory chain III. It has also been suggested that this protein plays a role in cytokinesis. Mutations in this gene cause mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2012]

TTC19 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex III deficiency nuclear type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.016).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042697.2. 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
	ZSWIM7	NM_001042697.2	MANE Select	c.-30C>T		5_prime_UTR	Exon 1 of 5	NP_001036162.1	Q19AV6
	ZSWIM7	NM_001042698.2		c.-30C>T		5_prime_UTR	Exon 1 of 6	NP_001036163.1	Q19AV6
	TTC19	NM_017775.4	MANE Select	c.-225G>A		upstream_gene	N/A	NP_060245.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM7	ENST00000399277.6	TSL:1 MANE Select	c.-30C>T		5_prime_UTR	Exon 1 of 5	ENSP00000382218.1	Q19AV6
	ZSWIM7	ENST00000472495.5	TSL:1	c.-30C>T		5_prime_UTR	Exon 1 of 6	ENSP00000419138.1	Q19AV6
	ZSWIM7	ENST00000486706.6	TSL:1	n.-30C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000463327.1	J3QS31

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000632 AC: 1 AN: 158304 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000823

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000354 AC: 5 AN: 1413198 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2 AN XY: 699130

African (AFR) AF: 0.00 AC: 0 AN: 32188

American (AMR) AF: 0.00 AC: 0 AN: 38112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25288

East Asian (EAS) AF: 0.0000273 AC: 1 AN: 36628

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1088626

Other (OTH) AF: 0.00 AC: 0 AN: 58568

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.96
PhyloP100		-0.25
PromoterAI		0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs779218631; hg19: chr17-15902938;