chr22-25029006-C-T

Variant names:

• chr22-25029006-C-T
• rs554100016
• NM_001145206.2:c.1007C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001145206.2(KIAA1671):​c.1007C>T​(p.Pro336Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,510,140 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (4 hom.)
• Consequence: KIAA1671 NM_001145206.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.635
• Publications: 0 publications found

Genes affected

KIAA1671 (HGNC:29345): (KIAA1671)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015227675).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145206.2. 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
	KIAA1671	NM_001145206.2	MANE Select	c.1007C>T	p.Pro336Leu	missense	Exon 3 of 13	NP_001138678.1	Q9BY89-1
	KIAA1671	NM_001386930.1		c.1007C>T	p.Pro336Leu	missense	Exon 3 of 12	NP_001373859.1
	KIAA1671	NM_001386932.1		c.1007C>T	p.Pro336Leu	missense	Exon 3 of 13	NP_001373861.1	Q9BY89-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1671	ENST00000358431.8	TSL:1 MANE Select	c.1007C>T	p.Pro336Leu	missense	Exon 3 of 13	ENSP00000351207.3	Q9BY89-1
	KIAA1671	ENST00000406486.8	TSL:5	c.1007C>T	p.Pro336Leu	missense	Exon 4 of 14	ENSP00000385152.3	Q9BY89-1
	KIAA1671	ENST00000910712.1		c.1007C>T	p.Pro336Leu	missense	Exon 4 of 14	ENSP00000580771.1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000339 AC: 460 AN: 1357768 Hom.: 4 Cov.: 51 AF XY: 0.000473 AC XY: 315 AN XY: 665926

African (AFR) AF: 0.000100 AC: 3 AN: 29914

American (AMR) AF: 0.0000363 AC: 1 AN: 27584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22406

East Asian (EAS) AF: 0.00 AC: 0 AN: 35340

South Asian (SAS) AF: 0.00582 AC: 422 AN: 72462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48144

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5474

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1060466

Other (OTH) AF: 0.000554 AC: 31 AN: 55978

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152372 Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21 AN XY: 74508

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.7
DANN	Benign	0.51
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.64
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.029
Sift	Benign	0.18	T
Sift4G	Uncertain	0.023	D
Polyphen		0.047	B
Vest4		0.14
MutPred		0.19		Loss of sheet (P = 0.0104)
MVP		0.099
ClinPred		0.11	T
GERP RS		1.0
Varity_R		0.036
gMVP		0.044
Mutation Taster		=100/0	polymorphism

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: rs554100016; hg19: chr22-25424973; COSMIC: COSV64449485; COSMIC: COSV64449485;