chr14-96456401-A-G

Variant names:

• chr14-96456401-A-G
• rs74090310
• NM_152327.5:c.1153A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152327.5(AK7):​c.1153A>G​(p.Lys385Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00508 in 1,613,880 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (194 hom., cov: 30)
  • Exomes 𝑓: 0.0027 (179 hom.)
• Consequence: AK7 NM_152327.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.46
• Publications: 7 publications found

Genes affected

AK7 (HGNC:20091): (adenylate kinase 7) This gene encodes a member of the adenylate kinase family of enzymes. The encoded enzyme is a phosphotransferase that catalyzes the reversible phosphorylation of adenine nucleotides. This enzyme plays a role in energy homeostasis of the cell. Alternative splicing results in multiple transcript variants. Mutations in the mouse gene are associated with primary ciliary dyskinesia. [provided by RefSeq, Apr 2017]

RPL23AP10 (HGNC:19804): (ribosomal protein L23a pseudogene 10)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022706687).
• BP6: Variant 14-96456401-A-G is Benign according to our data. Variant chr14-96456401-A-G is described in ClinVar as Benign. ClinVar VariationId is 402362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152327.5. 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
	AK7	NM_152327.5	MANE Select	c.1153A>G	p.Lys385Glu	missense	Exon 11 of 18	NP_689540.2	Q96M32
	AK7	NM_001350888.2		c.1153A>G	p.Lys385Glu	missense	Exon 11 of 17	NP_001337817.1
	AK7	NM_001350890.2		c.1153A>G	p.Lys385Glu	missense	Exon 11 of 17	NP_001337819.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK7	ENST00000267584.9	TSL:1 MANE Select	c.1153A>G	p.Lys385Glu	missense	Exon 11 of 18	ENSP00000267584.4	Q96M32
	AK7	ENST00000856706.1		c.1237A>G	p.Lys413Glu	missense	Exon 12 of 19	ENSP00000526765.1
	AK7	ENST00000856705.1		c.1153A>G	p.Lys385Glu	missense	Exon 11 of 17	ENSP00000526764.1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4172 AN: 152146 Hom.: 193 Cov.: 30

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00696 AC: 1751 AN: 251422 AF XY: 0.00500

Gnomad AFR exome AF: 0.0934

Gnomad AMR exome AF: 0.00509

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00274 AC: 4009 AN: 1461616 Hom.: 179 Cov.: 33 AF XY: 0.00233 AC XY: 1693 AN XY: 727128

African (AFR) AF: 0.0946 AC: 3163 AN: 33452

American (AMR) AF: 0.00629 AC: 281 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5764

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1111830

Other (OTH) AF: 0.00684 AC: 413 AN: 60388

GnomAD4 genome AF: 0.0275 AC: 4184 AN: 152264 Hom.: 194 Cov.: 30 AF XY: 0.0258 AC XY: 1924 AN XY: 74460

African (AFR) AF: 0.0948 AC: 3937 AN: 41530

American (AMR) AF: 0.0116 AC: 177 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68016

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.00981 Hom.: 132

Bravo AF: 0.0312

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0946 AC: 417

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00848 AC: 1030

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.9
DANN	Benign	0.53
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00056	N
LIST_S2	Benign	0.071	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N
PhyloP100		3.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.068
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.21
MPC		0.26
ClinPred		0.00040	T
GERP RS		3.0
Varity_R		0.061
gMVP		0.37
Mutation Taster		=96/4	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: rs74090310; hg19: chr14-96922738;