16-8884346-G-A

Position:

• chr16-8884346-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001395433.1(LITAFD):​c.-10G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00723 in 399,124 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (8 hom.)
• Consequence: LITAFD NM_001395433.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

Genes affected

LITAFD (HGNC:53927): (LITAF domain containing) Predicted to enable metal ion binding activity. Predicted to be located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-8884346-G-A is Benign according to our data. Variant chr16-8884346-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1675613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LITAFD	NM_001395433.1	c.-10G>A		5_prime_UTR_variant	3/4	ENST00000636296.2	NP_001382362.1
LITAFD	NM_001395434.1	c.-10G>A		5_prime_UTR_variant	3/4		NP_001382363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LITAFD	ENST00000636296.2	c.-10G>A		5_prime_UTR_variant	3/4	5	NM_001395433.1	ENSP00000490685	P1
LITAFD	ENST00000637237.1	c.-10G>A		5_prime_UTR_variant	3/4	5		ENSP00000490446	P1
LITAFD	ENST00000637929.1	c.-10G>A		5_prime_UTR_variant	3/4	5		ENSP00000489792

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 1037 AN: 152202 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00874

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00749 AC: 1849 AN: 246804 Hom.: 8 Cov.: 0 AF XY: 0.00738 AC XY: 923 AN XY: 125104

Gnomad4 AFR exome AF: 0.00139

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.0242

Gnomad4 NFE exome AF: 0.00757

Gnomad4 OTH exome AF: 0.00690

GnomAD4 genome AF: 0.00681 AC: 1037 AN: 152320 Hom.: 7 Cov.: 32 AF XY: 0.00742 AC XY: 553 AN XY: 74480

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0270

Gnomad4 NFE AF: 0.00875

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00943 Hom.: 1

Bravo AF: 0.00459

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

USP7: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149150494; hg19: chr16-8978203;