rs544184

Positions:

• chr11-112084759-G-A
• chr11-112084759-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393047.8(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 ENST00000393047.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NKAPD1	NM_018195.4	c.*1787G>A		3_prime_UTR_variant	6/6	ENST00000393047.8	NP_060665.3
TIMM8B	NM_012459.4			downstream_gene_variant		ENST00000504148.3	NP_036591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKAPD1	ENST00000393047.8	c.*1787G>A		3_prime_UTR_variant	6/6	1	NM_018195.4	ENSP00000376767	P1
TIMM8B	ENST00000504148.3			downstream_gene_variant		1	NM_012459.4	ENSP00000422122	P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 76665 AN: 147172 Hom.: 21764 Cov.: 26

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.: 73 Cov.: 0 AF XY: 0.563 AC XY: 143 AN XY: 254

Gnomad4 FIN exome AF: 0.594

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.521 AC: 76670 AN: 147220 Hom.: 21762 Cov.: 26 AF XY: 0.521 AC XY: 37280 AN XY: 71578

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.569

Alfa AF: 0.570 Hom.: 7970

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
DANN	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs544184; hg19: chr11-111955483; COSMIC: COSV54778628; COSMIC: COSV54778628;