7-6183649-T-C

Variant names:

• chr7-6183649-T-C
• rs10240988
• NM_004227.4:c.249+3401A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004227.4(CYTH3):​c.249+3401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,056 control chromosomes in the GnomAD database, including 5,056 homozygotes. 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: 𝑓 0.24 (5056 hom., cov: 32)
• Consequence: CYTH3 NM_004227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

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.249+3401A>G		intron	N/A	NP_004218.1
	CYTH3	NM_001367580.1		c.-929+3401A>G		intron	N/A	NP_001354509.1
	CYTH3	NM_001367581.1		c.-476+3401A>G		intron	N/A	NP_001354510.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYTH3	ENST00000350796.8	TSL:1 MANE Select	c.249+3401A>G		intron	N/A	ENSP00000297044.7
	CYTH3	ENST00000898314.1		c.387+3401A>G		intron	N/A	ENSP00000568373.1
	CYTH3	ENST00000898313.1		c.342+3401A>G		intron	N/A	ENSP00000568372.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36222 AN: 151938 Hom.: 5051 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.238 AC: 36233 AN: 152056 Hom.: 5056 Cov.: 32 AF XY: 0.238 AC XY: 17723 AN XY: 74328

African (AFR) AF: 0.387 AC: 16040 AN: 41460

American (AMR) AF: 0.183 AC: 2788 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3472

East Asian (EAS) AF: 0.0725 AC: 375 AN: 5174

South Asian (SAS) AF: 0.140 AC: 675 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2452 AN: 10558

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13047 AN: 67988

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.198 Hom.: 13905

Bravo AF: 0.239

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.088
DANN	Benign	0.40
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10240988; hg19: chr7-6223280;