chr11-112082853-A-G

Variant names:

• chr11-112082853-A-G
• NM_018195.4:c.763A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018195.4(NKAPD1):​c.763A>G​(p.Arg255Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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)
• Consequence: NKAPD1 NM_018195.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

NKAPD1 (HGNC:25569): (NKAP domain containing 1) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08411673).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018195.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAPD1	NM_018195.4	MANE Select	c.763A>G	p.Arg255Gly	missense	Exon 6 of 6	NP_060665.3
	NKAPD1	NM_001082969.2		c.763A>G	p.Arg255Gly	missense	Exon 6 of 6	NP_001076438.1
	NKAPD1	NM_001082970.2		c.760A>G	p.Arg254Gly	missense	Exon 6 of 6	NP_001076439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAPD1	ENST00000393047.8	TSL:1 MANE Select	c.763A>G	p.Arg255Gly	missense	Exon 6 of 6	ENSP00000376767.3
	NKAPD1	ENST00000420986.6	TSL:1	c.760A>G	p.Arg254Gly	missense	Exon 6 of 6	ENSP00000402208.2
	NKAPD1	ENST00000280352.13	TSL:2	c.760A>G	p.Arg254Gly	missense	Exon 6 of 6	ENSP00000339076.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.3
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.054
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.042	D
Polyphen		0.0	B
Vest4		0.081
MutPred		0.24		Gain of loop (P = 0.0045)
MVP		0.082
MPC		0.25
ClinPred		0.28	T
GERP RS		3.4
Varity_R		0.089
gMVP		0.13
Mutation Taster		=80/20	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

hg19: chr11-111953577;