chr16-67281106-A-C

Variant names:

• chr16-67281106-A-C
• NM_001129729.3:c.735A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001129729.3(PLEKHG4):​c.735A>C​(p.Ala245Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLEKHG4 NM_001129729.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• Publications: 0 publications found

Genes affected

PLEKHG4 (HGNC:24501): (pleckstrin homology and RhoGEF domain containing G4) The protein encoded by this gene can function as a guanine nucleotide exchange factor (GEF) and may play a role in intracellular signaling and cytoskeleton dynamics at the Golgi apparatus. Polymorphisms in the region of this gene have been found to be associated with spinocerebellar ataxia in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 16-67281106-A-C is Benign according to our data. Variant chr16-67281106-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3389194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129729.3. 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
	PLEKHG4	NM_001129729.3	MANE Select	c.735A>C	p.Ala245Ala	synonymous	Exon 5 of 22	NP_001123201.1	A0A024R6X4
	PLEKHG4	NM_001129727.3		c.735A>C	p.Ala245Ala	synonymous	Exon 6 of 23	NP_001123199.1	Q58EX7-1
	PLEKHG4	NM_001129728.2		c.735A>C	p.Ala245Ala	synonymous	Exon 5 of 22	NP_001123200.1	A0A024R6X4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG4	ENST00000379344.8	TSL:1 MANE Select	c.735A>C	p.Ala245Ala	synonymous	Exon 5 of 22	ENSP00000368649.3	Q58EX7-1
	PLEKHG4	ENST00000450733.5	TSL:1	c.492A>C	p.Ala164Ala	synonymous	Exon 3 of 20	ENSP00000398030.1	Q58EX7-2
	PLEKHG4	ENST00000393966.1	TSL:1	n.*320A>C		non_coding_transcript_exon	Exon 3 of 10	ENSP00000462601.1	Q58EX7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.7
DANN	Benign	0.63
PhyloP100		-1.2

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

hg19: chr16-67315009;