chr5-94417312-C-T

Variant names:

• chr5-94417312-C-T
• rs29910
• NM_001145678.3:c.2551G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001145678.3(KIAA0825):​c.2551G>A​(p.Ala851Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,549,286 control chromosomes in the GnomAD database, including 61,666 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4575 hom., cov: 33)
  • Exomes 𝑓: 0.28 (57091 hom.)
• Consequence: KIAA0825 NM_001145678.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.169
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024483502).
• BP6: Variant 5-94417312-C-T is Benign according to our data. Variant chr5-94417312-C-T is described in ClinVar as Benign. ClinVar VariationId is 1300066.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 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.2551G>A	p.Ala851Thr	missense	Exon 15 of 21	NP_001139150.1	A0A804HHT9
	KIAA0825	NM_001385712.1		c.2566G>A	p.Ala856Thr	missense	Exon 16 of 22	NP_001372641.1	A0A994J718
	KIAA0825	NM_001388325.1		c.2566G>A	p.Ala856Thr	missense	Exon 15 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.2551G>A	p.Ala851Thr	missense	Exon 15 of 21	ENSP00000506760.1	A0A804HHT9
	KIAA0825	ENST00000504117.1	TSL:1	n.1413G>A		non_coding_transcript_exon	Exon 9 of 9
	KIAA0825	ENST00000703867.1		c.2566G>A	p.Ala856Thr	missense	Exon 15 of 21	ENSP00000515512.1	A0A994J718

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35373 AN: 151872 Hom.: 4580 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.231

GnomAD2 exomes AF: 0.240 AC: 37493 AN: 155990 AF XY: 0.246

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.0771

Gnomad FIN exome AF: 0.290

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.280 AC: 390981 AN: 1397296 Hom.: 57091 Cov.: 33 AF XY: 0.280 AC XY: 192842 AN XY: 688992

African (AFR) AF: 0.153 AC: 4830 AN: 31558

American (AMR) AF: 0.142 AC: 5059 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 8075 AN: 25132

East Asian (EAS) AF: 0.0682 AC: 2431 AN: 35642

South Asian (SAS) AF: 0.248 AC: 19663 AN: 79138

European-Finnish (FIN) AF: 0.283 AC: 13933 AN: 49228

Middle Eastern (MID) AF: 0.305 AC: 1730 AN: 5680

European-Non Finnish (NFE) AF: 0.297 AC: 319697 AN: 1077332

Other (OTH) AF: 0.269 AC: 15563 AN: 57902

GnomAD4 genome AF: 0.233 AC: 35374 AN: 151990 Hom.: 4575 Cov.: 33 AF XY: 0.229 AC XY: 17023 AN XY: 74294

African (AFR) AF: 0.151 AC: 6250 AN: 41484

American (AMR) AF: 0.172 AC: 2628 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1088 AN: 3470

East Asian (EAS) AF: 0.0724 AC: 375 AN: 5178

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4820

European-Finnish (FIN) AF: 0.281 AC: 2972 AN: 10560

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20133 AN: 67916

Other (OTH) AF: 0.235 AC: 496 AN: 2114

Alfa AF: 0.273 Hom.: 27743

Bravo AF: 0.219

TwinsUK AF: 0.298 AC: 1105

ALSPAC AF: 0.302 AC: 1165

ESP6500AA AF: 0.148 AC: 205

ESP6500EA AF: 0.295 AC: 940

ExAC AF: 0.243 AC: 5858

Asia WGS AF: 0.186 AC: 644 AN: 3474

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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.17
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.057
Sift	Benign	0.30	T
Sift4G	Benign	0.46	T
Polyphen		0.26	B
Vest4		0.029
ClinPred		0.020	T
GERP RS		3.6
Varity_R		0.039
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs29910; hg19: chr5-93753017; COSMIC: COSV56956346;