chr4-39086721-A-G

Variant names:

• chr4-39086721-A-G
• rs35141484
• NM_015990.5:c.1107A>G

Variant summary

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

The NM_015990.5(KLHL5):​c.1107A>G​(p.Ala369Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,800 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: 0.0000014 (0 hom.)
• Consequence: KLHL5 NM_015990.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 0 publications found

Genes affected

KLHL5 (HGNC:6356): (kelch like family member 5) Predicted to enable actin binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000249207 (HGNC:58761):

LOC105374418 (HGNC:):

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=-0.71).
• BP7: Synonymous conserved (PhyloP=-1.33 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015990.5. 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
	KLHL5	NM_015990.5	MANE Select	c.1107A>G	p.Ala369Ala	synonymous	Exon 5 of 11	NP_057074.4
	KLHL5	NM_001007075.2		c.1107A>G	p.Ala369Ala	synonymous	Exon 6 of 12	NP_001007076.1	Q7Z6D5
	KLHL5	NM_199039.4		c.924A>G	p.Ala308Ala	synonymous	Exon 4 of 10	NP_950240.3	A0A804C9D6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL5	ENST00000504108.7	TSL:2 MANE Select	c.1107A>G	p.Ala369Ala	synonymous	Exon 5 of 11	ENSP00000423897.2	Q96PQ7-6
	KLHL5	ENST00000381930.8	TSL:1	c.1107A>G	p.Ala369Ala	synonymous	Exon 5 of 10	ENSP00000371355.4	A0A804CHP1
	KLHL5	ENST00000261425.7	TSL:1	c.1107A>G	p.Ala369Ala	synonymous	Exon 6 of 12	ENSP00000261425.3	Q96PQ7-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458800 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725930

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109320

Other (OTH) AF: 0.0000166 AC: 1 AN: 60298

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.60
PhyloP100		-1.3

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: rs35141484; hg19: chr4-39088341;