dbSNP rs544184: NKAPD1:c.*1787G>A (chr11-112084759-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018195.4(NKAPD1):c.*1787G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 147,654 control chromosomes in the GnomAD database, including 21,835 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 21762 hom., cov: 26)

Exomes 𝑓: 0.59 ( 73 hom. )

Consequence

NKAPD1
NM_018195.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

11 publications found

Variant links:

Genes affected

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

NKAPD1 links:

TIMM8B (HGNC:11818): (translocase of inner mitochondrial membrane 8 homolog B) This gene encodes a member of a well-conserved family of proteins with similarity to yeast Tim mitochondrial import proteins. This gene is encoded by a nuclear gene and is transported into the intermembrane space of the mitochondrion. When formed into complexes, these proteins guide membrane-spanning proteins across the mitochondrial intermembrane space before they are added into the mitochondrial inner membrane. This gene is adjacent to succinate dehydrogenase, subunit D (SDHD), in which mutations have been found in affected members of families with hereditary paraganglioma.[provided by RefSeq, Aug 2009]

TIMM8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAPD1	NM_018195.4 link	c.*1787G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000393047.8	NP_060665.3	A0A024R3H5
TIMM8B	NM_012459.4 link	c.*536C>T		downstream_gene_variant		ENST00000504148.3	NP_036591.3	Q9Y5J9G3XAN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKAPD1	ENST00000393047.8 link	c.*1787G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_018195.4	ENSP00000376767.3		Q6ZUT1-2
TIMM8B	ENST00000504148.3 link	c.*536C>T		downstream_gene_variant		1	NM_012459.4	ENSP00000422122.2		Q9Y5J9

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

76665

AN:

147172

Hom.:

21764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.588

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.600

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.569

GnomAD4 exome

AF:

0.594

AC:

258

AN:

434

Hom.:

Cov.:

AF XY:

0.563

AC XY:

143

AN XY:

254

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.594

AC:

247

AN:

416

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.521

AC:

76670

AN:

147220

Hom.:

21762

Cov.:

AF XY:

0.521

AC XY:

37280

AN XY:

71578

show subpopulations

African (AFR)

AF:

0.254

AC:

9897

AN:

38968

American (AMR)

AF:

0.588

AC:

8751

AN:

14882

Ashkenazi Jewish (ASJ)

AF:

0.681

AC:

2353

AN:

3456

East Asian (EAS)

AF:

0.422

AC:

2085

AN:

4944

South Asian (SAS)

AF:

0.598

AC:

2808

AN:

4692

European-Finnish (FIN)

AF:

0.657

AC:

6338

AN:

9654

Middle Eastern (MID)

AF:

0.590

AC:

158

AN:

268

European-Non Finnish (NFE)

AF:

0.633

AC:

42700

AN:

67412

Other (OTH)

AF:

0.569

AC:

1170

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

1596

3192

4787

6383

7979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.570

Hom.:

9904

Bravo

AF:

0.488

Asia WGS

AF:

0.512

AC:

1778

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.0

(source)

DANN

Benign

0.53

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over