7-6190493-G-A

Variant names:

• chr7-6190493-G-A
• rs11978706
• NM_004227.4:c.73C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004227.4(CYTH3):​c.73C>T​(p.Leu25Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,361,212 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: 30)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CYTH3 NM_004227.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 2 publications found

Genes affected

CYTH3 (HGNC:9504): (cytohesin 3) This gene encodes a member of the PSCD (pleckstrin homology, Sec7 and coiled-coil domains) family. PSCD family members have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. This encoded protein is involved in the control of Golgi structure and function, and it may have a physiological role in regulating ADP-ribosylation factor protein 6 (ARF) functions, in addition to acting on ARF1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.427 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004227.4. 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
	CYTH3	NM_004227.4	MANE Select	c.73C>T	p.Leu25Leu	synonymous	Exon 2 of 13	NP_004218.1	O43739-2
	CYTH3	NM_001367580.1		c.-1105C>T		5_prime_UTR	Exon 2 of 13	NP_001354509.1	B7Z2V9
	CYTH3	NM_001367581.1		c.-652C>T		5_prime_UTR	Exon 2 of 14	NP_001354510.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYTH3	ENST00000350796.8	TSL:1 MANE Select	c.73C>T	p.Leu25Leu	synonymous	Exon 2 of 13	ENSP00000297044.7	O43739-2
	CYTH3	ENST00000898314.1		c.211C>T	p.Leu71Leu	synonymous	Exon 3 of 14	ENSP00000568373.1
	CYTH3	ENST00000898313.1		c.166C>T	p.Leu56Leu	synonymous	Exon 3 of 14	ENSP00000568372.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1361212 Hom.: 0 Cov.: 34 AF XY: 0.00000298 AC XY: 2 AN XY: 671860

African (AFR) AF: 0.00 AC: 0 AN: 30102

American (AMR) AF: 0.00 AC: 0 AN: 29836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24454

East Asian (EAS) AF: 0.00 AC: 0 AN: 34798

South Asian (SAS) AF: 0.00 AC: 0 AN: 75380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5570

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1067492

Other (OTH) AF: 0.00 AC: 0 AN: 56586

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.43

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: rs11978706; hg19: chr7-6230124;