rs11978706

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-6190493-G-A
• chr7-6190493-G-C
• chr7-6190493-G-T

Variant summary

Our verdict is Likely benign. Variant got -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

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

Verdict is Likely_benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTH3	NM_004227.4	c.73C>T	p.Leu25Leu	synonymous_variant	Exon 2 of 13	ENST00000350796.8	NP_004218.1
CYTH3	NM_001367580.1	c.-1105C>T		5_prime_UTR_variant	Exon 2 of 13		NP_001354509.1
CYTH3	NM_001367581.1	c.-652C>T		5_prime_UTR_variant	Exon 2 of 14		NP_001354510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTH3	ENST00000350796.8	c.73C>T	p.Leu25Leu	synonymous_variant	Exon 2 of 13	1	NM_004227.4	ENSP00000297044.7
CYTH3	ENST00000482460.1	n.210C>T		non_coding_transcript_exon_variant	Exon 2 of 5	3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs11978706; hg19: chr7-6230124;