5-94396280-A-G

Variant names:

• chr5-94396280-A-G
• rs308207
• NM_001145678.3:c.3117T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001145678.3(KIAA0825):​c.3117T>C​(p.Ser1039Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 1,551,326 control chromosomes in the GnomAD database, including 670,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.94 (67688 hom., cov: 32)
  • Exomes 𝑓: 0.93 (602620 hom.)
• Consequence: KIAA0825 NM_001145678.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.350
• Publications: 14 publications found

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 Gene-Disease associations (from GenCC):

• polydactyly, postaxial, type a10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-94396280-A-G is Benign according to our data. Variant chr5-94396280-A-G is described in ClinVar as Benign. ClinVar VariationId is 1300065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145678.3. 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
	KIAA0825	NM_001145678.3	MANE Select	c.3117T>C	p.Ser1039Ser	synonymous	Exon 17 of 21	NP_001139150.1	A0A804HHT9
	KIAA0825	NM_001385712.1		c.3132T>C	p.Ser1044Ser	synonymous	Exon 18 of 22	NP_001372641.1	A0A994J718
	KIAA0825	NM_001388325.1		c.3132T>C	p.Ser1044Ser	synonymous	Exon 17 of 21	NP_001375254.1	A0A994J718

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0825	ENST00000682413.1	MANE Select	c.3117T>C	p.Ser1039Ser	synonymous	Exon 17 of 21	ENSP00000506760.1	A0A804HHT9
	KIAA0825	ENST00000703867.1		c.3132T>C	p.Ser1044Ser	synonymous	Exon 17 of 21	ENSP00000515512.1	A0A994J718
	KIAA0825	ENST00000513200.7	TSL:5	c.3117T>C	p.Ser1039Ser	synonymous	Exon 16 of 20	ENSP00000424618.2	Q8IV33-1

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143370 AN: 152152 Hom.: 67623 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.944

GnomAD2 exomes AF: 0.937 AC: 146736 AN: 156588 AF XY: 0.936

Gnomad AFR exome AF: 0.985

Gnomad AMR exome AF: 0.961

Gnomad ASJ exome AF: 0.889

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.894

Gnomad NFE exome AF: 0.924

Gnomad OTH exome AF: 0.929

GnomAD4 exome AF: 0.928 AC: 1298217 AN: 1399056 Hom.: 602620 Cov.: 48 AF XY: 0.928 AC XY: 640347 AN XY: 689986

African (AFR) AF: 0.985 AC: 31107 AN: 31586

American (AMR) AF: 0.959 AC: 34190 AN: 35658

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 22365 AN: 25158

East Asian (EAS) AF: 1.00 AC: 35714 AN: 35728

South Asian (SAS) AF: 0.950 AC: 75248 AN: 79176

European-Finnish (FIN) AF: 0.894 AC: 44057 AN: 49262

Middle Eastern (MID) AF: 0.922 AC: 5249 AN: 5692

European-Non Finnish (NFE) AF: 0.923 AC: 996111 AN: 1078778

Other (OTH) AF: 0.934 AC: 54176 AN: 58018

GnomAD4 genome AF: 0.942 AC: 143495 AN: 152270 Hom.: 67688 Cov.: 32 AF XY: 0.943 AC XY: 70169 AN XY: 74442

African (AFR) AF: 0.984 AC: 40886 AN: 41556

American (AMR) AF: 0.947 AC: 14475 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3087 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5180

South Asian (SAS) AF: 0.954 AC: 4602 AN: 4826

European-Finnish (FIN) AF: 0.896 AC: 9500 AN: 10604

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62724 AN: 68028

Other (OTH) AF: 0.945 AC: 1997 AN: 2114

Alfa AF: 0.927 Hom.: 130763

Bravo AF: 0.949

Asia WGS AF: 0.978 AC: 3403 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	KIAA0825-related disorder (1)
-	-	1	Polydactyly, postaxial, type a10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs308207; hg19: chr5-93731985; COSMIC: COSV70247362;