NM_001145678.3:c.3516C>T

Variant names:

• chr5-94386345-G-A
• rs29913
• NM_001145678.3:c.3516C>T

Variant summary

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

The NM_001145678.3(KIAA0825):​c.3516C>T​(p.Ile1172Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,348 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. Synonymous variant affecting the same amino acid position (i.e. I1172I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KIAA0825 NM_001145678.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526
• Publications: 0 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: 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=-0.66).
• BP7: Synonymous conserved (PhyloP=0.526 with no splicing effect.

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.3516C>T	p.Ile1172Ile	synonymous	Exon 19 of 21	NP_001139150.1	A0A804HHT9
	KIAA0825	NM_001385712.1		c.3531C>T	p.Ile1177Ile	synonymous	Exon 20 of 22	NP_001372641.1	A0A994J718
	KIAA0825	NM_001388325.1		c.3531C>T	p.Ile1177Ile	synonymous	Exon 19 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.3516C>T	p.Ile1172Ile	synonymous	Exon 19 of 21	ENSP00000506760.1	A0A804HHT9
	KIAA0825	ENST00000703867.1		c.3531C>T	p.Ile1177Ile	synonymous	Exon 19 of 21	ENSP00000515512.1	A0A994J718
	KIAA0825	ENST00000513200.7	TSL:5	c.3516C>T	p.Ile1172Ile	synonymous	Exon 18 of 20	ENSP00000424618.2	Q8IV33-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399348 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690176

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35696

South Asian (SAS) AF: 0.00 AC: 0 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078788

Other (OTH) AF: 0.00 AC: 0 AN: 58088

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		0.53

Splicing

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

Other links and lift over

dbSNP: rs29913; hg19: chr5-93722050;