11-65718256-T-G

Variant names:

• chr11-65718256-T-G
• rs521678
• NM_032193.4:c.*1527A>C

Variant summary

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

The NM_032193.4(RNASEH2C):​c.*1527A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 231,548 control chromosomes in the GnomAD database, including 91,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59041 hom., cov: 32)
  • Exomes 𝑓: 0.90 (32070 hom.)
• Consequence: RNASEH2C NM_032193.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.452
• Publications: 11 publications found

Genes affected

RNASEH2C (HGNC:24116): (ribonuclease H2 subunit C) This gene encodes a ribonuclease H subunit that can cleave ribonucleotides from RNA:DNA duplexes. Mutations in this gene cause Aicardi-Goutieres syndrome-3, a disease that causes severe neurologic dysfunction. A pseudogene for this gene has been identified on chromosome Y, near the sex determining region Y (SRY) gene. [provided by RefSeq, Jul 2008]

KAT5 (HGNC:5275): (lysine acetyltransferase 5) The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

KAT5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-65718256-T-G is Benign according to our data. Variant chr11-65718256-T-G is described in ClinVar as Benign. ClinVar VariationId is 305334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032193.4. 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
	RNASEH2C	NM_032193.4	MANE Select	c.*1527A>C		3_prime_UTR	Exon 4 of 4	NP_115569.2
	KAT5	NM_182710.3	MANE Select	c.1265-334T>G		intron	N/A	NP_874369.1
	KAT5	NM_006388.4		c.1166-334T>G		intron	N/A	NP_006379.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2C	ENST00000308418.10	TSL:1 MANE Select	c.*1527A>C		3_prime_UTR	Exon 4 of 4	ENSP00000308193.5
	KAT5	ENST00000341318.9	TSL:1 MANE Select	c.1265-334T>G		intron	N/A	ENSP00000340330.4
	KAT5	ENST00000377046.7	TSL:1	c.1166-334T>G		intron	N/A	ENSP00000366245.3

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133747 AN: 152074 Hom.: 58993 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.880

GnomAD4 exome AF: 0.896 AC: 71105 AN: 79356 Hom.: 32070 Cov.: 2 AF XY: 0.890 AC XY: 36685 AN XY: 41196

African (AFR) AF: 0.823 AC: 2271 AN: 2758

American (AMR) AF: 0.878 AC: 4042 AN: 4606

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 2246 AN: 2532

East Asian (EAS) AF: 0.901 AC: 4898 AN: 5438

South Asian (SAS) AF: 0.740 AC: 5127 AN: 6930

European-Finnish (FIN) AF: 0.913 AC: 2973 AN: 3258

Middle Eastern (MID) AF: 0.909 AC: 269 AN: 296

European-Non Finnish (NFE) AF: 0.922 AC: 45126 AN: 48938

Other (OTH) AF: 0.903 AC: 4153 AN: 4600

GnomAD4 genome AF: 0.880 AC: 133856 AN: 152192 Hom.: 59041 Cov.: 32 AF XY: 0.877 AC XY: 65257 AN XY: 74398

African (AFR) AF: 0.830 AC: 34419 AN: 41486

American (AMR) AF: 0.880 AC: 13453 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3109 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4624 AN: 5172

South Asian (SAS) AF: 0.720 AC: 3472 AN: 4822

European-Finnish (FIN) AF: 0.902 AC: 9568 AN: 10602

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62328 AN: 68026

Other (OTH) AF: 0.878 AC: 1855 AN: 2112

Alfa AF: 0.904 Hom.: 235547

Bravo AF: 0.878

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Aicardi-Goutieres syndrome 3 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-0.45
PromoterAI		0.0027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs521678; hg19: chr11-65485727;