11-112084759-G-A

Variant names:

• chr11-112084759-G-A
• rs544184
• NM_018195.4:c.*1787G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 11 publications found

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

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAPD1	NM_018195.4	MANE Select	c.*1787G>A		3_prime_UTR	Exon 6 of 6	NP_060665.3
	NKAPD1	NM_001082969.2		c.*1787G>A		3_prime_UTR	Exon 6 of 6	NP_001076438.1	Q6ZUT1-2
	NKAPD1	NM_001082970.2		c.*1787G>A		3_prime_UTR	Exon 6 of 6	NP_001076439.1	Q6ZUT1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAPD1	ENST00000393047.8	TSL:1 MANE Select	c.*1787G>A		3_prime_UTR	Exon 6 of 6	ENSP00000376767.3	Q6ZUT1-2
	NKAPD1	ENST00000968797.1		c.*1787G>A		3_prime_UTR	Exon 6 of 6	ENSP00000638856.1
	NKAPD1	ENST00000862992.1		c.*1787G>A		3_prime_UTR	Exon 6 of 6	ENSP00000533051.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.594 AC: 247 AN: 416

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 7 AN: 14

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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